S Phase (Homo sapiens)

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30, 37-39, 571140, 592611, 531146253656192555, 5816, 31, 441815, 5249, 543712215617, 5043137, 26, 33, 44, 45, 5915, 24, 34, 5316, 12, 29, 30, 39...3515, 52, 5319342564, 11, 15, 2827, 32, 56234718, 22, 445337, 411RFCHeteropentamer:RNAprimer-DNAprimer:origin duplex[nucleoplasm]phospho(T286)-CyclinD1:Cdk4[nucleoplasm]Cohesin:PDS5:WAPAL:ChromosomalArm [nucleoplasm]SCF(Skp2):Cks1complex[nucleoplasm]Processive complex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]ubiquitin[nucleoplasm]p21/p27[nucleoplasm]ubiquitinated Cdc6[cytosol]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]SCF(Skp2) complex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]CyclinA:phospho-Cdk2(Thr160)complex[nucleoplasm]SCF(Skp2):Cks1complex[nucleoplasm]pre-replicativecomplex[nucleoplasm]Processive complex[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]CyclinE/A:Cdk2:phospho-p27/p21[nucleoplasm]Processive complex[nucleoplasm]Ac-Cohesin:PDS5:WAPAL:ChromosomalArm [nucleoplasm]PCNA homotrimer[nucleoplasm]Mcm2-7 complex[nucleoplasm]RFC Heteropentamer[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]Mcm4,6,7 complex[nucleoplasm]Orc2 associated withMCM8 [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]Cohesin:PDS5:WAPAL[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]phospho-p27/p21[nucleoplasm]DNA polymeraseepsilon[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]Ac-Cohesin Complex[nucleoplasm]RPA heterotrimer[nucleoplasm]pre-replicativecomplex (Orc1-minus)[nucleoplasm]Ub [cytosol]Cyclin E/A:Cdk2[nucleoplasm]CDC6:ORC:origincomplex[nucleoplasm]Cohesin:PDS5:WAPAL:Centromere[nucleoplasm]CDT1:CDC6:ORC:origincomplex[nucleoplasm]Cyclin A:Cdk2complex [cytosol]DNA polymerasealpha:primase[nucleoplasm]Cyclin E/A[nucleoplasm]Cyclin E/A:Cdk2[nucleoplasm]Cyclin A:Cdk1substrate proteins[nucleoplasm]SCF(Skp2) complex[nucleoplasm]Cohesin Complex[nucleoplasm]Cyclin E/A[nucleoplasm]CyclinA:phospho-Cdk2(Thr160)complex[nucleoplasm]Ac-Cohesin:PDS5:WAPAL:Centromere[nucleoplasm]Cyclin E/A[nucleoplasm]Processivecomplex:Okazakifragments:RemainingFlap [nucleoplasm]Cyclin D1:Cdk4[nucleoplasm]26S proteasome[nucleoplasm]Mcm2-7 complex[nucleoplasm]CyclinA:phospho-Cdk2(Tyr15) [nucleoplasm]CyclinE/A:Cdk2:phospho-p27/p21[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]Cyclin E/A:Cdk2[nucleoplasm]RPA heterotrimer[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]PCNA homotrimer[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]SCF(Skp2):Cks1complex[nucleoplasm]RPA heterotrimer[nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]Ac-Cohesin Complex[nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]SisterCentromeres:Ac-Cohesin:PDS5:CDCA5:WAPAL[chromosome,centromeric region]DNA polymerasealpha:primase:DNApolymerasealpha:origin complex[nucleoplasm]Processive complex[nucleoplasm]CyclinE/A:Cdk2:phospho-p27/p21[nucleoplasm]Ac-Cohesin:PDS5:WAPAL[nucleoplasm]Processivecomplex:Okazakifragment:Flap:RPAheterotrimer[nucleoplasm]Ub [cytosol]PCNA homotrimer[nucleoplasm]CyclinE/A:Cdk2:p27/p21complex[nucleoplasm]Cyclin E/A:Cdk2[nucleoplasm]multi-ubiquitinatedphospho-(T286)Cyclin D1 [cytosol]Centromere:Ac-Cohesin:PDS5:CDCA5:WAPAL[chromosome,centromeric region]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]ORC:origin[nucleoplasm]Processivecomplex:Okazakifragment:Flap:RPAheterotrimer[nucleoplasm]Ub [cytosol]Ac-Cohesin Complex[chromosome]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]SCF(Skp2) complex[nucleoplasm]Unwinding complex atreplication fork[nucleoplasm]Cyclin A:Cdk2complex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]PDS5 [nucleoplasm]p21/p27[nucleoplasm]CyclinA:Cdk2:phospho-p27/p21complex[nucleoplasm]phospho-p27/p21[nucleoplasm]Mcm2-7 complex[nucleoplasm]Myc/Max heterodimer[nucleoplasm]Cyclin E/A[nucleoplasm]Orc2 associated withMCM8 [nucleoplasm]Processive complex[nucleoplasm]nucleoplasmDNA polymerasealpha:primase[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]PCNA homotrimer[nucleoplasm]phospho(T286)-CyclinD1:Cdk4 [cytosol]ubiquitinated Orc1[cytosol]CyclinA:Cdk2:p21/p27complex[nucleoplasm]Ac-Cohesin:PDS5:WAPAL[nucleoplasm]Processivecomplex:Okazakifragment complex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]Processivecomplex:Okazakifragment:Flap[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]CyclinA:Cdk2:substratecomplex[nucleoplasm]ubiquitin[nucleoplasm]CyclinE/A:Cdk2:multiubiquitinatedphospho-p27/p21:SCF(Skp2):Cks1complex[nucleoplasm]CyclinA:Cdk2:phosphorylatedsubstrate complex[nucleoplasm]ubiquitinated Orc1[nucleoplasm]PDS5 [nucleoplasm]Cohesin Complex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]RFC Heteropentamer[nucleoplasm]RFCHeteropentamer:RNAprimer-DNAprimer:origin duplex[nucleoplasm]CDK [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]RFC Heteropentamer[nucleoplasm]DNA polymeraseepsilon[nucleoplasm]Cyclin A:Cdk2complex[nucleoplasm]SCF(Skp2) complex[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]DNA polymerasealpha:primase[nucleoplasm]Processivecomplex:Okazakifragment:Flap[nucleoplasm]Processivecomplex:Okazakifragment:Flap:RPAheterotrimer:dna2[nucleoplasm]PCNA homotrimer[nucleoplasm]PDS5 [chromosome,centromeric region]Cohesin:PDS5:WAPAL[nucleoplasm]RFCHeteropentamer:RNAprimer-DNAprimer:originduplex:PCNAhomotrimer[nucleoplasm]Ac-Cohesin Complex[chromosome,centromeric region]PDS5 [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]Processive complex[nucleoplasm]PCNA homotrimer[nucleoplasm]PCNA homotrimer[nucleoplasm]Processive complex[nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]Ac-Cohesin:PDS5:CDCA5:WAPAL[chromosome]Cyclin E/A[nucleoplasm]GINS complex[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]26S proteasome[cytosol]DNA Polymerase deltatetramer[nucleoplasm]CyclinE/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1complex[nucleoplasm]Processivecomplex:nicked DNAfrom adjacentOkazaki fragments[nucleoplasm]Ac-Cohesin:PDS5:CDCA5:WAPAL[chromosome,centromeric region]phospho-p27/p21[nucleoplasm]CyclinE/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1complex[nucleoplasm]Mcm2-7 complex[nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]CyclinA:phospho-Cdk2(Thr160)complex[nucleoplasm]phospho-p27/p21[nucleoplasm]PDS5 [nucleoplasm]phosphorylatedCyclin A:Cdk2substrate proteins[nucleoplasm]Processivecomplex:Okazakifragment complex[nucleoplasm]Processivecomplex:Okazakifragment:Flap[nucleoplasm]DNA polymeraseepsilon:origincomplex[nucleoplasm]CAK [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplex[nucleoplasm]GINS complex[nucleoplasm]RNA primer-DNAprimer:originduplex:PCNA [nucleoplasm]RNA primer-DNAprimer:origin duplex[nucleoplasm]Cyclin A:Cdk2complex[nucleoplasm]Sister ChromosomalArms:Ac-Cohesin:PDS5:CDCA5:WAPAL[chromosome]PCNA homotrimer[nucleoplasm]PCNA homotrimer[nucleoplasm]PDS5 [chromosome]PCNA homotrimer[nucleoplasm]Cyclin E/A:Cdk2[nucleoplasm]Processivecomplex:Okazakifragment complex[nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]Processivecomplex:Okazakifragment complex[nucleoplasm]ORC1 [nucleoplasm]phospho(T286)-CyclinD1:Cdk4MCM5 [nucleoplasm]RFC5 [nucleoplasm]PRIM1 [nucleoplasm]PSMC1(2-440)[nucleoplasm]p-T286-CCND1PSMA6 [nucleoplasm]MCM4(1-863)[nucleoplasm]PRIM2 [nucleoplasm]ADPRFCHeteropentamer:RNAprimer-DNAprimer:originduplex:PCNAhomotrimerPOLD3 [nucleoplasm]PSMA5 [nucleoplasm]ATPSTAG1 [nucleoplasm]PDS5A [nucleoplasm]PRIM1 [nucleoplasm]PRIM2 [nucleoplasm]PCNA [nucleoplasm]SCF(Skp2):Cks1complexPRIM2 [nucleoplasm]MCM2 [nucleoplasm]RPS27A(1-76)[cytosol]STAG2 [chromosome,centromeric region]SMC1A [nucleoplasm]Sister ChromosomalArms:Ac-Cohesin:PDS5:CDCA5:WAPALUBC(381-456)[cytosol]UBC(609-684)[cytosol]POLD1 [nucleoplasm]SKP2 [nucleoplasm]PDS5B [nucleoplasm]CDKN1A [nucleoplasm]POLD4 [nucleoplasm]PCNA [nucleoplasm]STAG2 [nucleoplasm]PSMD13 [nucleoplasm]SCF(Skp2) complexCDC6 [nucleoplasm]POLD2 [nucleoplasm]POLA1 [nucleoplasm]SMC1A [nucleoplasm]GINS complexPSMB6 [cytosol]UBC(381-456)[cytosol]UBB(77-152)[cytosol]p-T286-CCND1[cytosol]Ac-Cohesin:PDS5:WAPAL:ChromosomalArmRAD21 [nucleoplasm]dATPUBC(1-76)[nucleoplasm]PSMD10 [cytosol]p-T160-CDK2[nucleoplasm]Ac-Cohesin:PDS5:WAPAL:CentromereCDC6 [cytosol]RNA primer-DNAprimer:origin duplexPDS5A [chromosome,centromeric region]UBC(533-608)[cytosol]PSMB5 [nucleoplasm]UBC(153-228)[cytosol]POLA2 [nucleoplasm]RFC1 [nucleoplasm]RPA3 [nucleoplasm]Ubiquitin ligaseRPA heterotrimerAc-CoAPSMD4(2-377)[nucleoplasm]Unwinding complex atreplication forkGINS2CyclinE/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1complexSKP2 [nucleoplasm]Cyclin D1:Cdk4PSMA4 [cytosol]ATPMCM8 [nucleoplasm]MCM4(1-863)[nucleoplasm]POLA2 [nucleoplasm]ORC5 [nucleoplasm]UBC(457-532)[nucleoplasm]CDKN1B [nucleoplasm]ORC6 [nucleoplasm]POLD1 [nucleoplasm]UBC(457-532)[cytosol]PSMB7 [cytosol]GINS4(1-223)[nucleoplasm]Cyclin A:Cdk2complexCDC45UBC(609-684)[cytosol]CDK2 [nucleoplasm]anaphase-promotingcomplex (APC)Cohesin:PDS5:WAPAL:ChromosomalArmRFC4 [nucleoplasm]UBC(305-380)[nucleoplasm]UBB(77-152)[cytosol]PRIM1 [nucleoplasm]SMC1A [nucleoplasm]Myc/Max heterodimerPOLA1 [nucleoplasm]RB1 [nucleoplasm]PSMB2 [nucleoplasm]MCM6 [nucleoplasm]RPA1 [nucleoplasm]MYC [nucleoplasm]RFC1 [nucleoplasm]PSMA3 [cytosol]UBC(229-304)[cytosol]GINS1 [nucleoplasm]CyclinA:Cdk2:p21/p27complexPOLA2 [nucleoplasm]POLE2 [nucleoplasm]ADPMitoticTelophase/CytokinesisPOLD4 [nucleoplasm]Cohesin:PDS5:WAPAL:CentromereMCM6 [nucleoplasm]PSME4 [cytosol]PSMC2 [cytosol]PSMD9 [nucleoplasm]CMPSMC3 [nucleoplasm]ATPMCM6 [nucleoplasm]UBC(381-456)[cytosol]PRIM1 [nucleoplasm]PDS5B [nucleoplasm]ubiquitinated Orc1STAG2 [nucleoplasm]POLD2 [nucleoplasm]AMPSKP1 [nucleoplasm]p-S130-CDKN1A[nucleoplasm]RPA1 [nucleoplasm]UBB(153-228)[nucleoplasm]ubiquitinated Cdc6PSMD11 [nucleoplasm]PSMB4 [cytosol]UBC(229-304)[nucleoplasm]CDK2 [cytosol]p-S130-CDKN1A[nucleoplasm]ORC4 [nucleoplasm]ATPPSMF1(2-271)[nucleoplasm]ADPMCM7 [nucleoplasm]POLD2 [nucleoplasm]POLA2 [nucleoplasm]26S proteasomePSME1 [nucleoplasm]MCM5 [nucleoplasm]NTPMNAT1 [nucleoplasm]pre-replicativecomplexMCM6 [nucleoplasm]POLD3 [nucleoplasm]RPS27A(1-76)[nucleoplasm]SMC1A [nucleoplasm]p-T286-CCND1[nucleoplasm]ubiquitinGINS2 [nucleoplasm]Cdc25 A/BPCNA [nucleoplasm]POLA1 [nucleoplasm]CDK2 [nucleoplasm]UBC(153-228)[nucleoplasm]Processivecomplex:nicked DNAfrom adjacentOkazaki fragmentsUBC(305-380)[nucleoplasm]UBC(153-228)[nucleoplasm]UBC(305-380)[cytosol]UBB(153-228)[cytosol]PDS5A [nucleoplasm]MCM7 [nucleoplasm]PSMC2 [nucleoplasm]SMC3 [nucleoplasm]UBA52(1-76)[nucleoplasm]UBC(381-456)[nucleoplasm]PRIM2 [nucleoplasm]Sister CentromereUBC(1-76) [cytosol]CKS1B [nucleoplasm]PCNA [nucleoplasm]PRIM2 [nucleoplasm]UBC(229-304)[cytosol]PSMC5 [cytosol]PRIM1 [nucleoplasm]UBB(153-228)[cytosol]RNA primer-DNAprimer:originduplex:PCNAPOLD3 [nucleoplasm]CDK2 [nucleoplasm]PSMD2 [nucleoplasm]POLA2 [nucleoplasm]PRIM1 [nucleoplasm]phospho(T286)-CyclinD1:Cdk4ORC2 [nucleoplasm]UBC(77-152)[cytosol]H2OPSMB9 [nucleoplasm]MCM5RFC1 [nucleoplasm]UbCyclinA:Cdk2:phosphorylatedsubstrate complexRFC2 [nucleoplasm]POLA2 [nucleoplasm]RFC HeteropentamerUBC(153-228)[cytosol]CyclinA:Cdk2:substratecomplexGINS4(1-223)CKS1B [nucleoplasm]Mitotic PrometaphaseMcm4,6,7 complexProcessivecomplex:Okazakifragments:RemainingFlapp-Y15-CDK2[nucleoplasm]dTTPPRIM1 [nucleoplasm]CDC45 [nucleoplasm]MCM2RFC3 [nucleoplasm]POLA1 [nucleoplasm]PDS5B [nucleoplasm]ATPPSMC6(2-389)[cytosol]UBC(77-152)[nucleoplasm]PSMB5 [cytosol]DNA2 [nucleoplasm]POLD4 [nucleoplasm]CDK7 [nucleoplasm]multi-ubiquitinatedphospho-(T286)Cyclin D1PSME3 [nucleoplasm]PSMC4 [nucleoplasm]PSMB4 [nucleoplasm]POLA1 [nucleoplasm]RFC4 [nucleoplasm]PSMA6 [cytosol]UBB(1-76) [cytosol]MCM2 [nucleoplasm]POLD2 [nucleoplasm]RPA2 [nucleoplasm]POLA1 [nucleoplasm]CCNH [nucleoplasm]Replication ForkADPWEE1CDT1 [nucleoplasm]2xAcK-SMC3[nucleoplasm]WAPAL [chromosome]PSF3pCDK2 [nucleoplasm]Processivecomplex:Okazakifragment:FlapPSMD4(2-377)[cytosol]CDK4(2-303)[nucleoplasm]DNA Polymerase deltatetramerUBB(153-228)[cytosol]POLD4 [nucleoplasm]CDKN1APOLD1 [nucleoplasm]PSMD8 [nucleoplasm]POLD2 [nucleoplasm]RAD21 [nucleoplasm]Cyclin A:Cdk2complexRFC5 [nucleoplasm]SKP1 [nucleoplasm]RFC3 [nucleoplasm]PSMA7(2-248)[nucleoplasm]UBC(1-76) [cytosol]CDT1 [nucleoplasm]RFCHeteropentamer:RNAprimer-DNAprimer:origin duplexATPPOLD1 [nucleoplasm]POLD3 [nucleoplasm]UBC(609-684)[cytosol]PDS5B [chromosome]PSME2 [cytosol]POLE [nucleoplasm]PSMB8 [nucleoplasm]PSMA2 [cytosol]PSMB6 [nucleoplasm]CDK2 [nucleoplasm]POLD3 [nucleoplasm]PRIM2 [nucleoplasm]FEN1ESCOMCM3 [nucleoplasm]PRIM2 [nucleoplasm]POLD1 [nucleoplasm]Processivecomplex:Okazakifragment complexRFC5 [nucleoplasm]PCNA [nucleoplasm]GINS1ORC1 [cytosol]PSMD8 [cytosol]PSMC1(2-440)[cytosol]ADPUBB(77-152)[nucleoplasm]PSMB8 [cytosol]SMC1A [chromosome,centromeric region]CyclinE/A:Cdk2:p27/p21complexPOLD1 [nucleoplasm]CDKN1A [nucleoplasm]RAD21 [chromosome,centromeric region]POLD2 [nucleoplasm]PSMF1(2-271)[cytosol]SKP1 [nucleoplasm]CDC25ACDK2 [nucleoplasm]UBC(77-152)[cytosol]MCM3 [nucleoplasm]DNA polymerasealpha:primaseFZR1 [nucleoplasm]LIG1CUL1 [nucleoplasm]ORC1 [nucleoplasm]PCNA [nucleoplasm]PCNA [nucleoplasm]PRIM2 [nucleoplasm]RNA primer:originduplex:DNApolymerasealpha:primasecomplexPOLD3 [nucleoplasm]UBC(77-152)[cytosol]CDKN1B [nucleoplasm]PSMB7 [nucleoplasm]PSMA1 [nucleoplasm]PRIM2 [nucleoplasm]PSMC6(2-389)[nucleoplasm]UBC(305-380)[cytosol]MCM8p-S130-CDKN1A[nucleoplasm]MCM7 [nucleoplasm]2xAcK-SMC3[nucleoplasm]CDC6PCNA [nucleoplasm]PRIM1 [nucleoplasm]PDS5B [chromosome,centromeric region]PSMB2 [cytosol]UBB(1-76) [cytosol]p-S130-CDKN1A[nucleoplasm]POLA1 [nucleoplasm]CyclinA:Cdk2:phospho-p27/p21complexUnwound forkUBC(1-76) [cytosol]CyclinA:phospho-Cdk2(Thr160)complexCDK2 [nucleoplasm]2xAcK-SMC3[chromosome]PRIM2 [nucleoplasm]POLA1 [nucleoplasm]CDKMCM2 [nucleoplasm]dGTPORC5 [nucleoplasm]dCTPADPPSMD1 [cytosol]MCM7 [nucleoplasm]RPS27A(1-76)[nucleoplasm]PRIM2 [nucleoplasm]PSMB3 [cytosol]STAG1 [nucleoplasm]PSMA3 [nucleoplasm]PSMB1 [cytosol]PSMD14 [nucleoplasm]ATPADPp-T187-CDKN1B[nucleoplasm]PDS5B [nucleoplasm]MCM5 [nucleoplasm]p-T286-CCND1[cytosol]POLA2 [nucleoplasm]WAPAL [nucleoplasm]POLD4 [nucleoplasm]PSMD2 [cytosol]26S proteasomeMAX(1-160)[nucleoplasm]Okazaki fragmentPSMA8 [cytosol]CDKN1B [nucleoplasm]PRIM2 [nucleoplasm]CUL1 [nucleoplasm]CKS1BPSMD1 [nucleoplasm]RPA2 [nucleoplasm]RAD21 [chromosome]ATPp-T286-CCND1RFC4 [nucleoplasm]p21/p27PRIM1 [nucleoplasm]WAPAL [chromosome,centromeric region]PSMD5 [nucleoplasm]SKP2 [nucleoplasm]PSMD9 [cytosol]UBC(1-76)[nucleoplasm]WAPAL [nucleoplasm]glycogen synthasekinase-3 betaUBA52(1-76)[cytosol]CyclinE/A:Cdk2:multiubiquitinatedphospho-p27/p21:SCF(Skp2):Cks1complexligated okazakifragmentp-T187-CDKN1B[nucleoplasm]CDCA5SMC1A [chromosome]MCM7 [nucleoplasm]UBC(609-684)[nucleoplasm]CDKN1APOLA2 [nucleoplasm]POLA1 [nucleoplasm]POLD1 [nucleoplasm]PSMB9 [cytosol]UBC(533-608)[cytosol]ORC3 [nucleoplasm]UBC(77-152)[nucleoplasm]STAG2 [nucleoplasm]WAPAL [nucleoplasm]CyclinA:phospho-Cdk2(Tyr15)CKS1B [nucleoplasm]ubiquitinated Orc1PDS5A [nucleoplasm]p-T160-CDK2[nucleoplasm]POLE2 [nucleoplasm]RPA3 [nucleoplasm]PSMD6(2-389)[cytosol]UBA52(1-76)[cytosol]PSMD7(2-324)[cytosol]PDS5A [chromosome]PSMD6(2-389)[nucleoplasm]Processivecomplex:Okazakifragment:Flap:RPAheterotrimer:dna2p-T187-CDKN1B[nucleoplasm]POLD2 [nucleoplasm]CDK2 [nucleoplasm]p-CDC6POLA2 [nucleoplasm]POLA1 [nucleoplasm]CUL1 [nucleoplasm]UBC(305-380)[cytosol]UBC(153-228)[cytosol]RPA3 [nucleoplasm]UBC(609-684)[nucleoplasm]PSMB10 [cytosol]MCM4(1-863)[nucleoplasm]UBA52(1-76)[nucleoplasm]PSMB3 [nucleoplasm]POLD2 [nucleoplasm]UBC(533-608)[nucleoplasm]SisterCentromeres:Ac-Cohesin:PDS5:CDCA5:WAPALPSMD3 [nucleoplasm]p-FZR1 [nucleoplasm]PSMD12 [cytosol]POLD4 [nucleoplasm]SKP2 [nucleoplasm]RFC3 [nucleoplasm]CAKPOLA2 [nucleoplasm]PDS5A [nucleoplasm]Cyclin E/A:Cdk2UBC(457-532)[nucleoplasm]PSME2 [nucleoplasm]UBC(381-456)[nucleoplasm]UMPPSMB1 [nucleoplasm]p-T187-CDKN1B[nucleoplasm]STAG1 [chromosome]RPS27A(1-76)[cytosol]PSMD14 [cytosol]MCM3CUL1 [nucleoplasm]DNA polymerasealpha:primase:DNApolymerasealpha:origin complexORC2 [nucleoplasm]SKP1 [nucleoplasm]RPS27A(1-76)[cytosol]PSMC5 [nucleoplasm]UBB(77-152)[nucleoplasm]CDKN1BPRIM1 [nucleoplasm]PSME1 [cytosol]PSMD5 [cytosol]PSMC4 [cytosol]CDK4(2-303)[cytosol]ORC4 [nucleoplasm]CDC6 [nucleoplasm]CDKN1BCDK2 [nucleoplasm]CDCA5 [chromosome]PRIM1 [nucleoplasm]PSMC3 [nucleoplasm]POLD3 [nucleoplasm]STAG1 [chromosome,centromeric region]CDCA5 [chromosome,centromeric region]MCM6 [nucleoplasm]UBB(1-76)[nucleoplasm]POLD4 [nucleoplasm]UBC(457-532)[cytosol]PSMA5 [cytosol]ORC3 [nucleoplasm]MCM8 [nucleoplasm]MCM3 [nucleoplasm]PSMA7(2-248)[cytosol]2xAcK-SMC3[chromosome,centromeric region]PSMB11 [cytosol]ATPPRIM1 [nucleoplasm]RAD21 [nucleoplasm]PSMD13 [cytosol]Sister ChromosomalArmADPMCM4(1-863)[nucleoplasm]POLA1 [nucleoplasm]CDK2CDKN1A [nucleoplasm]POLA2 [nucleoplasm]PSMB10 [nucleoplasm]MCM4(1-863)[nucleoplasm]RPA1 [nucleoplasm]GMPPCNA homotrimerCyclinE/A:Cdk2:phospho-p27/p21Cyclin ACDC6POLD3 [nucleoplasm]POLE [nucleoplasm]UBC(229-304)[nucleoplasm]MCM5 [nucleoplasm]p-T160-CDK2[nucleoplasm]UBC(533-608)[cytosol]MCM2 [nucleoplasm]p-T187-CDKN1B[nucleoplasm]PSMC3 [cytosol]PSMD11 [cytosol]STAG2 [chromosome]pre-replicativecomplex (Orc1-minus)UBB(1-76)[nucleoplasm]p-S130-CDKN1A[nucleoplasm]PSMA4 [nucleoplasm]POLA1 [nucleoplasm]STAG2 [nucleoplasm]PCNA [nucleoplasm]PCNA [nucleoplasm]PSMA1 [cytosol]PRIM1 [nucleoplasm]POLD1 [nucleoplasm]GINS4(1-223)[nucleoplasm]PSMD10 [nucleoplasm]UBA52(1-76)[cytosol]Processive complexp-S,T-ORC1PSMD3 [cytosol]GINS1 [nucleoplasm]POLA2 [nucleoplasm]CCND1 [nucleoplasm]POLA1 [nucleoplasm]UBB(77-152)[cytosol]UBB(1-76) [cytosol]RAD21 [nucleoplasm]DNA polymeraseepsilonPRIM2 [nucleoplasm]RFC2 [nucleoplasm]POLA2 [nucleoplasm]RFC2 [nucleoplasm]CDK4(2-303)[nucleoplasm]PRIM2 [nucleoplasm]DNA2PSMA2 [nucleoplasm]GINS2 [nucleoplasm]STAG1 [nucleoplasm]PSMD12 [nucleoplasm]MCM3 [nucleoplasm]POLD4 [nucleoplasm]PSME3 [cytosol]PSMD7(2-324)[nucleoplasm]p-RB1 [nucleoplasm]UBB(153-228)[nucleoplasm]PRIM1 [nucleoplasm]CoA-SHMcm2-7 complexORC6 [nucleoplasm]UBC(533-608)[nucleoplasm]Processivecomplex:Okazakifragment:Flap:RPAheterotrimerPOLA1 [nucleoplasm]PiRPA2 [nucleoplasm]UBC(457-532)[cytosol]STAG1 [nucleoplasm]POLA2 [nucleoplasm]WAPAL [nucleoplasm]UBC(229-304)[cytosol]5, 105119209481442119


Description

DNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues, the E type cyclins shared by the G1 and S phases, are destroyed and the levels of the mitotic cyclins rise.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=69242

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  5. Montagnoli A, Fiore F, Eytan E, Carrano AC, Draetta GF, Hershko A, Pagano M.; ''Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.''; PubMed Europe PMC Scholia
  6. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  7. Diehl JA, Zindy F, Sherr CJ.; ''Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
  8. Aprelikova O, Xiong Y, Liu ET.; ''Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by the CDK-activating kinase.''; PubMed Europe PMC Scholia
  9. Gu Y, Rosenblatt J, Morgan DO.; ''Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.''; PubMed Europe PMC Scholia
  10. Wu CL, Kirley SD, Xiao H, Chuang Y, Chung DC, Zukerberg LR.; ''Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.''; PubMed Europe PMC Scholia
  11. Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, Zhang P, Kim ST, Pan X, Qin J.; ''Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast.''; PubMed Europe PMC Scholia
  12. Benzeno S, Lu F, Guo M, Barbash O, Zhang F, Herman JG, Klein PS, Rustgi A, Diehl JA.; ''Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.''; PubMed Europe PMC Scholia
  13. Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
  14. Van Den Berg DJ, Francke U.; ''Roberts syndrome: a review of 100 cases and a new rating system for severity.''; PubMed Europe PMC Scholia
  15. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
  16. Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, De Baere E, Decroos C, Di Donato N, Ernst S, Francey LJ, Gyftodimou Y, Hirashima K, Hullings M, Ishikawa Y, Jaulin C, Kaur M, Kiyono T, Lombardi PM, Magnaghi-Jaulin L, Mortier GR, Nozaki N, Petersen MB, Seimiya H, Siu VM, Suzuki Y, Takagaki K, Wilde JJ, Willems PJ, Prigent C, Gillessen-Kaesbach G, Christianson DW, Kaiser FJ, Jackson LG, Hirota T, Krantz ID, Shirahige K.; ''HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.''; PubMed Europe PMC Scholia
  17. Xiang B, Chatti K, Qiu H, Lakshmi B, Krasnitz A, Hicks J, Yu M, Miller WT, Muthuswamy SK.; ''Brk is coamplified with ErbB2 to promote proliferation in breast cancer.''; PubMed Europe PMC Scholia
  18. Blomberg I, Hoffmann I.; ''Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases.''; PubMed Europe PMC Scholia
  19. Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A.; ''Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase.''; PubMed Europe PMC Scholia
  20. Bembenek J, Yu H.; ''Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a.''; PubMed Europe PMC Scholia
  21. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ.; ''The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.''; PubMed Europe PMC Scholia
  22. Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, Kayserili H, Basaran S, Skovby F, Hennekam RC, Uzielli ML, Schnur RE, Manouvrier S, Chang S, Blair E, Hurst JA, Forzano F, Meins M, Simola KO, Raas-Rothschild A, Schultz RA, McDaniel LD, Ozono K, Inui K, Zou H, Jabs EW.; ''The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity.''; PubMed Europe PMC Scholia
  23. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC.; ''Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.''; PubMed Europe PMC Scholia
  24. Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G.; ''Cyclin A is required at two points in the human cell cycle.''; PubMed Europe PMC Scholia
  25. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H.; ''p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.''; PubMed Europe PMC Scholia
  26. Whelan G, Kreidl E, Kreidl E, Wutz G, Egner A, Peters JM, Eichele G.; ''Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin.''; PubMed Europe PMC Scholia
  27. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M, Hershko A.; ''The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27.''; PubMed Europe PMC Scholia
  28. Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A.; ''Noncatalytic requirement for cyclin A-cdk2 in p27 turnover.''; PubMed Europe PMC Scholia
  29. DeGregori J, Kowalik T, Nevins JR.; ''Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.''; PubMed Europe PMC Scholia
  30. Jackman M, Kubota Y, den Elzen N, Hagting A, Pines J.; ''Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm.''; PubMed Europe PMC Scholia
  31. Guo Y, Yang K, Harwalkar J, Nye JM, Mason DR, Garrett MD, Hitomi M, Stacey DW.; ''Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis.''; PubMed Europe PMC Scholia
  32. Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP.; ''Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.''; PubMed Europe PMC Scholia
  33. Mitra J, Enders GH, Azizkhan-Clifford J, Lengel KL.; ''Dual regulation of the anaphase promoting complex in human cells by cyclin A-Cdk2 and cyclin A-Cdk1 complexes.''; PubMed Europe PMC Scholia
  34. Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro M.; ''Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.''; PubMed Europe PMC Scholia
  35. Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC, Helin K.; ''CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.''; PubMed Europe PMC Scholia
  36. Sarshad AA, Corcoran M, Al-Muzzaini B, Borgonovo-Brandter L, Von Euler A, Lamont D, Visa N, Percipalle P.; ''Glycogen synthase kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells.''; PubMed Europe PMC Scholia
  37. Hou F, Zou H.; ''Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion.''; PubMed Europe PMC Scholia
  38. Patel P, Asbach B, Shteyn E, Gomez C, Coltoff A, Bhuyan S, Tyner AL, Wagner R, Blain SW.; ''Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.''; PubMed Europe PMC Scholia
  39. Carrano AC, Eytan E, Hershko A, Pagano M.; ''SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.''; PubMed Europe PMC Scholia
  40. Rankin S, Ayad NG, Kirschner MW.; ''Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates.''; PubMed Europe PMC Scholia
  41. Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
118522view10:10, 28 May 2021EweitzOntology Term : 'S phase pathway' added !
115059view17:00, 25 January 2021ReactomeTeamReactome version 75
113503view11:58, 2 November 2020ReactomeTeamReactome version 74
112703view16:10, 9 October 2020ReactomeTeamReactome version 73
101618view11:48, 1 November 2018ReactomeTeamreactome version 66
101154view21:34, 31 October 2018ReactomeTeamreactome version 65
100681view20:07, 31 October 2018ReactomeTeamreactome version 64
100231view16:52, 31 October 2018ReactomeTeamreactome version 63
99783view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99337view12:47, 31 October 2018ReactomeTeamreactome version 62
93537view11:26, 9 August 2017ReactomeTeamreactome version 61
86636view09:22, 11 July 2016ReactomeTeamreactome version 56
83395view11:07, 18 November 2015ReactomeTeamVersion54
81589view13:07, 21 August 2015ReactomeTeamVersion53
77049view08:35, 17 July 2014ReactomeTeamFixed remaining interactions
76754view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76079view10:14, 11 June 2014ReactomeTeamRe-fixing comment source
75789view11:32, 10 June 2014ReactomeTeamReactome 48 Update
75139view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74786view08:52, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexREACT_2353 (Reactome)
26S proteasomeComplexREACT_7467 (Reactome)
2xAcK-SMC3

[chromosome,

centromeric region]
ProteinQ9UQE7 (Uniprot-TrEMBL)
2xAcK-SMC3 [chromosome]ProteinQ9UQE7 (Uniprot-TrEMBL)
2xAcK-SMC3 [nucleoplasm]ProteinQ9UQE7 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
Ac-Cohesin:PDS5:WAPAL:CentromereComplexREACT_152186 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmComplexREACT_151929 (Reactome)
CAKComplexREACT_5717 (Reactome)
CCND1 [nucleoplasm]ProteinP24385 (Uniprot-TrEMBL)
CCNH [nucleoplasm]ProteinP51946 (Uniprot-TrEMBL)
CDC25AProteinP30304 (Uniprot-TrEMBL)
CDC45 [nucleoplasm]ProteinO75419 (Uniprot-TrEMBL)
CDC45ProteinO75419 (Uniprot-TrEMBL)
CDC6 [cytosol]ProteinQ99741 (Uniprot-TrEMBL)
CDC6 [nucleoplasm]ProteinQ99741 (Uniprot-TrEMBL)
CDC6ProteinQ99741 (Uniprot-TrEMBL)
CDCA5 [chromosome, centromeric region]ProteinQ96FF9 (Uniprot-TrEMBL)
CDCA5 [chromosome]ProteinQ96FF9 (Uniprot-TrEMBL)
CDCA5ProteinQ96FF9 (Uniprot-TrEMBL)
CDK2 [cytosol]ProteinP24941 (Uniprot-TrEMBL)
CDK2 [nucleoplasm]ProteinP24941 (Uniprot-TrEMBL)
CDK2ProteinP24941 (Uniprot-TrEMBL)
CDK4(2-303) [cytosol]ProteinP11802 (Uniprot-TrEMBL)
CDK4(2-303) [nucleoplasm]ProteinP11802 (Uniprot-TrEMBL)
CDK7 [nucleoplasm]ProteinP50613 (Uniprot-TrEMBL)
CDKN1A [nucleoplasm]ProteinP38936 (Uniprot-TrEMBL)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CDKN1B [nucleoplasm]ProteinP46527 (Uniprot-TrEMBL)
CDKN1BProteinP46527 (Uniprot-TrEMBL)
CDKComplexREACT_5476 (Reactome)
CDT1 [nucleoplasm]ProteinQ9H211 (Uniprot-TrEMBL)
CKS1B [nucleoplasm]ProteinP61024 (Uniprot-TrEMBL)
CKS1BProteinP61024 (Uniprot-TrEMBL)
CMPMetaboliteCHEBI:17361 (ChEBI)
CUL1 [nucleoplasm]ProteinQ13616 (Uniprot-TrEMBL)
Cdc25 A/BREACT_9277 (Reactome)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
Cohesin:PDS5:WAPAL:CentromereComplexREACT_151885 (Reactome)
Cohesin:PDS5:WAPAL:Chromosomal ArmComplexREACT_150643 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
ComplexREACT_9335 (Reactome)
Cyclin

A:Cdk2:phospho-p27/p21

complex
ComplexREACT_9145 (Reactome)
Cyclin

A:Cdk2:phosphorylated

substrate complex
ComplexREACT_9299 (Reactome)
Cyclin

A:Cdk2:substrate

complex
ComplexREACT_9192 (Reactome)
Cyclin

A:phospho-Cdk2(Thr160)

complex
ComplexREACT_9292 (Reactome)
Cyclin

A:phospho-Cdk2(Tyr

15)
ComplexREACT_9202 (Reactome)
Cyclin

E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1

complex
ComplexREACT_9266 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
ComplexREACT_9314 (Reactome)
Cyclin

E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1

complex
ComplexREACT_9193 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21ComplexREACT_9321 (Reactome)
Cyclin A:Cdk2 complexComplexREACT_4932 (Reactome)
Cyclin A:Cdk2 complexComplexREACT_9350 (Reactome)
Cyclin AProteinREACT_6541 (Reactome)
Cyclin D1:Cdk4ComplexREACT_2478 (Reactome)
Cyclin E/A:Cdk2ComplexREACT_9091 (Reactome)
DNA Polymerase delta tetramerComplexREACT_5801 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase

alpha:origin complex
ComplexREACT_3167 (Reactome)
DNA polymerase alpha:primaseComplexREACT_3725 (Reactome)
DNA polymerase epsilonComplexREACT_4621 (Reactome)
DNA2 [nucleoplasm]ProteinP51530 (Uniprot-TrEMBL)
DNA2ProteinP51530 (Uniprot-TrEMBL)
ESCOProteinREACT_151079 (Reactome)
FEN1ProteinP39748 (Uniprot-TrEMBL)
FZR1 [nucleoplasm]ProteinQ9UM11 (Uniprot-TrEMBL)
GINS complexComplexREACT_7704 (Reactome)
GINS1 [nucleoplasm]ProteinQ14691 (Uniprot-TrEMBL)
GINS1ProteinQ14691 (Uniprot-TrEMBL)
GINS2 [nucleoplasm]ProteinQ9Y248 (Uniprot-TrEMBL)
GINS2ProteinQ9Y248 (Uniprot-TrEMBL)
GINS4(1-223) [nucleoplasm]ProteinQ9BRT9 (Uniprot-TrEMBL)
GINS4(1-223)ProteinQ9BRT9 (Uniprot-TrEMBL)
GMPMetaboliteCHEBI:17345 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
LIG1ProteinP18858 (Uniprot-TrEMBL)
MAX(1-160) [nucleoplasm]ProteinP61244 (Uniprot-TrEMBL)
MCM2 [nucleoplasm]ProteinP49736 (Uniprot-TrEMBL)
MCM2ProteinP49736 (Uniprot-TrEMBL)
MCM3 [nucleoplasm]ProteinP25205 (Uniprot-TrEMBL)
MCM3ProteinP25205 (Uniprot-TrEMBL)
MCM4(1-863) [nucleoplasm]ProteinP33991 (Uniprot-TrEMBL)
MCM5 [nucleoplasm]ProteinP33992 (Uniprot-TrEMBL)
MCM5ProteinP33992 (Uniprot-TrEMBL)
MCM6 [nucleoplasm]ProteinQ14566 (Uniprot-TrEMBL)
MCM7 [nucleoplasm]ProteinP33993 (Uniprot-TrEMBL)
MCM8 [nucleoplasm]ProteinQ9UJA3 (Uniprot-TrEMBL)
MCM8ProteinQ9UJA3 (Uniprot-TrEMBL)
MNAT1 [nucleoplasm]ProteinP51948 (Uniprot-TrEMBL)
MYC [nucleoplasm]ProteinP01106 (Uniprot-TrEMBL)
Mcm2-7 complexComplexREACT_4763 (Reactome)
Mcm4,6,7 complexComplexREACT_3276 (Reactome)
Mitotic Telophase/CytokinesisPathwayWP2765 (WikiPathways) In this final phase of mitosis, new membranes are formed around two sets of chromatids and two daughter cells are formed. The chromosomes and the spindle fibers disperse, and the fiber ring around the center of the cell, composed of actin, contracts, pinching the cell into two daughter cells.
Mitotic PrometaphasePathwayWP2652 (WikiPathways) The dissolution of the nuclear membrane marks the beginning of the prometaphase. Kinetochores are created when proteins attach to the centromeres. Microtubules then attach at the kinetochores, and the chromosomes begin to move to the metaphase plate.
Myc/Max heterodimerComplexREACT_9233 (Reactome)
NTPMetaboliteREACT_4491 (Reactome)
ORC1 [cytosol]ProteinQ13415 (Uniprot-TrEMBL)
ORC1 [nucleoplasm]ProteinQ13415 (Uniprot-TrEMBL)
ORC2 [nucleoplasm]ProteinQ13416 (Uniprot-TrEMBL)
ORC3 [nucleoplasm]ProteinQ9UBD5 (Uniprot-TrEMBL)
ORC4 [nucleoplasm]ProteinO43929 (Uniprot-TrEMBL)
ORC5 [nucleoplasm]ProteinO43913 (Uniprot-TrEMBL)
ORC6 [nucleoplasm]ProteinQ9Y5N6 (Uniprot-TrEMBL)
Okazaki fragmentREACT_4386 (Reactome)
PCNA [nucleoplasm]ProteinP12004 (Uniprot-TrEMBL)
PCNA homotrimerComplexREACT_2542 (Reactome)
PDS5A [chromosome, centromeric region]ProteinQ29RF7 (Uniprot-TrEMBL)
PDS5A [chromosome]ProteinQ29RF7 (Uniprot-TrEMBL)
PDS5A [nucleoplasm]ProteinQ29RF7 (Uniprot-TrEMBL)
PDS5B [chromosome, centromeric region]ProteinQ9NTI5 (Uniprot-TrEMBL)
PDS5B [chromosome]ProteinQ9NTI5 (Uniprot-TrEMBL)
PDS5B [nucleoplasm]ProteinQ9NTI5 (Uniprot-TrEMBL)
POLA1 [nucleoplasm]ProteinP09884 (Uniprot-TrEMBL)
POLA2 [nucleoplasm]ProteinQ14181 (Uniprot-TrEMBL)
POLD1 [nucleoplasm]ProteinP28340 (Uniprot-TrEMBL)
POLD2 [nucleoplasm]ProteinP49005 (Uniprot-TrEMBL)
POLD3 [nucleoplasm]ProteinQ15054 (Uniprot-TrEMBL)
POLD4 [nucleoplasm]ProteinQ9HCU8 (Uniprot-TrEMBL)
POLE [nucleoplasm]ProteinQ07864 (Uniprot-TrEMBL)
POLE2 [nucleoplasm]ProteinP56282 (Uniprot-TrEMBL)
PRIM1 [nucleoplasm]ProteinP49642 (Uniprot-TrEMBL)
PRIM2 [nucleoplasm]ProteinP49643 (Uniprot-TrEMBL)
PSF3pREACT_7682 (Reactome)
PSMA1 [cytosol]ProteinP25786 (Uniprot-TrEMBL)
PSMA1 [nucleoplasm]ProteinP25786 (Uniprot-TrEMBL)
PSMA2 [cytosol]ProteinP25787 (Uniprot-TrEMBL)
PSMA2 [nucleoplasm]ProteinP25787 (Uniprot-TrEMBL)
PSMA3 [cytosol]ProteinP25788 (Uniprot-TrEMBL)
PSMA3 [nucleoplasm]ProteinP25788 (Uniprot-TrEMBL)
PSMA4 [cytosol]ProteinP25789 (Uniprot-TrEMBL)
PSMA4 [nucleoplasm]ProteinP25789 (Uniprot-TrEMBL)
PSMA5 [cytosol]ProteinP28066 (Uniprot-TrEMBL)
PSMA5 [nucleoplasm]ProteinP28066 (Uniprot-TrEMBL)
PSMA6 [cytosol]ProteinP60900 (Uniprot-TrEMBL)
PSMA6 [nucleoplasm]ProteinP60900 (Uniprot-TrEMBL)
PSMA7(2-248) [cytosol]ProteinO14818 (Uniprot-TrEMBL)
PSMA7(2-248) [nucleoplasm]ProteinO14818 (Uniprot-TrEMBL)
PSMA8 [cytosol]ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 [cytosol]ProteinP20618 (Uniprot-TrEMBL)
PSMB1 [nucleoplasm]ProteinP20618 (Uniprot-TrEMBL)
PSMB10 [cytosol]ProteinP40306 (Uniprot-TrEMBL)
PSMB10 [nucleoplasm]ProteinP40306 (Uniprot-TrEMBL)
PSMB11 [cytosol]ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 [cytosol]ProteinP49721 (Uniprot-TrEMBL)
PSMB2 [nucleoplasm]ProteinP49721 (Uniprot-TrEMBL)
PSMB3 [cytosol]ProteinP49720 (Uniprot-TrEMBL)
PSMB3 [nucleoplasm]ProteinP49720 (Uniprot-TrEMBL)
PSMB4 [cytosol]ProteinP28070 (Uniprot-TrEMBL)
PSMB4 [nucleoplasm]ProteinP28070 (Uniprot-TrEMBL)
PSMB5 [cytosol]ProteinP28074 (Uniprot-TrEMBL)
PSMB5 [nucleoplasm]ProteinP28074 (Uniprot-TrEMBL)
PSMB6 [cytosol]ProteinP28072 (Uniprot-TrEMBL)
PSMB6 [nucleoplasm]ProteinP28072 (Uniprot-TrEMBL)
PSMB7 [cytosol]ProteinQ99436 (Uniprot-TrEMBL)
PSMB7 [nucleoplasm]ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 [cytosol]ProteinP28062 (Uniprot-TrEMBL)
PSMB8 [nucleoplasm]ProteinP28062 (Uniprot-TrEMBL)
PSMB9 [cytosol]ProteinP28065 (Uniprot-TrEMBL)
PSMB9 [nucleoplasm]ProteinP28065 (Uniprot-TrEMBL)
PSMC1(2-440) [cytosol]ProteinP62191 (Uniprot-TrEMBL)
PSMC1(2-440) [nucleoplasm]ProteinP62191 (Uniprot-TrEMBL)
PSMC2 [cytosol]ProteinP35998 (Uniprot-TrEMBL)
PSMC2 [nucleoplasm]ProteinP35998 (Uniprot-TrEMBL)
PSMC3 [cytosol]ProteinP17980 (Uniprot-TrEMBL)
PSMC3 [nucleoplasm]ProteinP17980 (Uniprot-TrEMBL)
PSMC4 [cytosol]ProteinP43686 (Uniprot-TrEMBL)
PSMC4 [nucleoplasm]ProteinP43686 (Uniprot-TrEMBL)
PSMC5 [cytosol]ProteinP62195 (Uniprot-TrEMBL)
PSMC5 [nucleoplasm]ProteinP62195 (Uniprot-TrEMBL)
PSMC6(2-389) [cytosol]ProteinP62333 (Uniprot-TrEMBL)
PSMC6(2-389) [nucleoplasm]ProteinP62333 (Uniprot-TrEMBL)
PSMD1 [cytosol]ProteinQ99460 (Uniprot-TrEMBL)
PSMD1 [nucleoplasm]ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 [cytosol]ProteinO75832 (Uniprot-TrEMBL)
PSMD10 [nucleoplasm]ProteinO75832 (Uniprot-TrEMBL)
PSMD11 [cytosol]ProteinO00231 (Uniprot-TrEMBL)
PSMD11 [nucleoplasm]ProteinO00231 (Uniprot-TrEMBL)
PSMD12 [cytosol]ProteinO00232 (Uniprot-TrEMBL)
PSMD12 [nucleoplasm]ProteinO00232 (Uniprot-TrEMBL)
PSMD13 [cytosol]ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD13 [nucleoplasm]ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 [cytosol]ProteinO00487 (Uniprot-TrEMBL)
PSMD14 [nucleoplasm]ProteinO00487 (Uniprot-TrEMBL)
PSMD2 [cytosol]ProteinQ13200 (Uniprot-TrEMBL)
PSMD2 [nucleoplasm]ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 [cytosol]ProteinO43242 (Uniprot-TrEMBL)
PSMD3 [nucleoplasm]ProteinO43242 (Uniprot-TrEMBL)
PSMD4(2-377) [cytosol]ProteinP55036 (Uniprot-TrEMBL)
PSMD4(2-377) [nucleoplasm]ProteinP55036 (Uniprot-TrEMBL)
PSMD5 [cytosol]ProteinQ16401 (Uniprot-TrEMBL)
PSMD5 [nucleoplasm]ProteinQ16401 (Uniprot-TrEMBL)
PSMD6(2-389) [cytosol]ProteinQ15008 (Uniprot-TrEMBL)
PSMD6(2-389) [nucleoplasm]ProteinQ15008 (Uniprot-TrEMBL)
PSMD7(2-324) [cytosol]ProteinP51665 (Uniprot-TrEMBL)
PSMD7(2-324) [nucleoplasm]ProteinP51665 (Uniprot-TrEMBL)
PSMD8 [cytosol]ProteinP48556 (Uniprot-TrEMBL)
PSMD8 [nucleoplasm]ProteinP48556 (Uniprot-TrEMBL)
PSMD9 [cytosol]ProteinO00233 (Uniprot-TrEMBL)
PSMD9 [nucleoplasm]ProteinO00233 (Uniprot-TrEMBL)
PSME1 [cytosol]ProteinQ06323 (Uniprot-TrEMBL)
PSME1 [nucleoplasm]ProteinQ06323 (Uniprot-TrEMBL)
PSME2 [cytosol]ProteinQ9UL46 (Uniprot-TrEMBL)
PSME2 [nucleoplasm]ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 [cytosol]ProteinP61289 (Uniprot-TrEMBL)
PSME3 [nucleoplasm]ProteinP61289 (Uniprot-TrEMBL)
PSME4 [cytosol]ProteinQ14997 (Uniprot-TrEMBL)
PSMF1(2-271) [cytosol]ProteinQ92530 (Uniprot-TrEMBL)
PSMF1(2-271) [nucleoplasm]ProteinQ92530 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
Processive

complex:Okazaki

fragment complex
ComplexREACT_5537 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
ComplexREACT_3597 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
ComplexREACT_4699 (Reactome)
Processive

complex:Okazaki

fragment:Flap
ComplexREACT_4984 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
ComplexREACT_4338 (Reactome)
Processive

complex:nicked DNA from adjacent

Okazaki fragments
ComplexREACT_4371 (Reactome)
Processive complexComplexREACT_3120 (Reactome)
RAD21 [chromosome, centromeric region]ProteinO60216 (Uniprot-TrEMBL)
RAD21 [chromosome]ProteinO60216 (Uniprot-TrEMBL)
RAD21 [nucleoplasm]ProteinO60216 (Uniprot-TrEMBL)
RB1 [nucleoplasm]ProteinP06400 (Uniprot-TrEMBL)
RFC

Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA

homotrimer
ComplexREACT_5474 (Reactome)
RFC

Heteropentamer:RNA primer-DNA

primer:origin duplex
ComplexREACT_5241 (Reactome)
RFC HeteropentamerComplexREACT_4881 (Reactome)
RFC1 [nucleoplasm]ProteinP35251 (Uniprot-TrEMBL)
RFC2 [nucleoplasm]ProteinP35250 (Uniprot-TrEMBL)
RFC3 [nucleoplasm]ProteinP40938 (Uniprot-TrEMBL)
RFC4 [nucleoplasm]ProteinP35249 (Uniprot-TrEMBL)
RFC5 [nucleoplasm]ProteinP40937 (Uniprot-TrEMBL)
RNA primer-DNA

primer:origin

duplex:PCNA
ComplexREACT_4810 (Reactome)
RNA primer-DNA primer:origin duplexComplexREACT_5497 (Reactome)
RNA primer:origin

duplex:DNA polymerase alpha:primase

complex
ComplexREACT_5709 (Reactome)
RPA heterotrimerComplexREACT_3427 (Reactome)
RPA1 [nucleoplasm]ProteinP27694 (Uniprot-TrEMBL)
RPA2 [nucleoplasm]ProteinP15927 (Uniprot-TrEMBL)
RPA3 [nucleoplasm]ProteinP35244 (Uniprot-TrEMBL)
RPS27A(1-76) [cytosol]ProteinP62979 (Uniprot-TrEMBL)
RPS27A(1-76) [nucleoplasm]ProteinP62979 (Uniprot-TrEMBL)
Replication ForkREACT_7812 (Reactome)
SCF(Skp2) complexComplexREACT_9339 (Reactome)
SCF(Skp2):Cks1 complexComplexREACT_9182 (Reactome)
SKP1 [nucleoplasm]ProteinP63208 (Uniprot-TrEMBL)
SKP2 [nucleoplasm]ProteinQ13309 (Uniprot-TrEMBL)
SMC1A [chromosome, centromeric region]ProteinQ14683 (Uniprot-TrEMBL)
SMC1A [chromosome]ProteinQ14683 (Uniprot-TrEMBL)
SMC1A [nucleoplasm]ProteinQ14683 (Uniprot-TrEMBL)
SMC3 [nucleoplasm]ProteinQ9UQE7 (Uniprot-TrEMBL)
STAG1 [chromosome, centromeric region]ProteinQ8WVM7 (Uniprot-TrEMBL)
STAG1 [chromosome]ProteinQ8WVM7 (Uniprot-TrEMBL)
STAG1 [nucleoplasm]ProteinQ8WVM7 (Uniprot-TrEMBL)
STAG2 [chromosome, centromeric region]ProteinQ8N3U4 (Uniprot-TrEMBL)
STAG2 [chromosome]ProteinQ8N3U4 (Uniprot-TrEMBL)
STAG2 [nucleoplasm]ProteinQ8N3U4 (Uniprot-TrEMBL)
Sister Centromeres:Ac-Cohesin:PDS5:CDCA5:WAPALComplexREACT_151874 (Reactome)
Sister CentromereREACT_151483 (Reactome)
Sister Chromosomal ArmREACT_150847 (Reactome)
Sister Chromosomal Arms:Ac-Cohesin:PDS5:CDCA5:WAPALComplexREACT_150576 (Reactome)
UBA52(1-76) [cytosol]ProteinP62987 (Uniprot-TrEMBL)
UBA52(1-76) [nucleoplasm]ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) [nucleoplasm]ProteinP0CG47 (Uniprot-TrEMBL)
UBB(1-76) [cytosol]ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) [cytosol]ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) [nucleoplasm]ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) [cytosol]ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) [nucleoplasm]ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(1-76) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) [cytosol]ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) [nucleoplasm]ProteinP0CG48 (Uniprot-TrEMBL)
UMPMetaboliteCHEBI:16695 (ChEBI)
UbProteinREACT_3316 (Reactome)
Ubiquitin ligaseREACT_4282 (Reactome)
Unwinding complex at replication forkComplexREACT_7007 (Reactome)
Unwound forkREACT_7610 (Reactome)
WAPAL [chromosome, centromeric region]ProteinQ7Z5K2 (Uniprot-TrEMBL)
WAPAL [chromosome]ProteinQ7Z5K2 (Uniprot-TrEMBL)
WAPAL [nucleoplasm]ProteinQ7Z5K2 (Uniprot-TrEMBL)
WEE1ProteinP30291 (Uniprot-TrEMBL)
anaphase-promoting complex (APC)REACT_3388 (Reactome)
dATPMetaboliteCHEBI:16284 (ChEBI)
dCTPMetaboliteCHEBI:16311 (ChEBI)
dGTPMetaboliteCHEBI:16497 (ChEBI)
dTTPMetaboliteCHEBI:18077 (ChEBI)
glycogen synthase kinase-3 betaREACT_3846 (Reactome)
ligated okazaki fragmentREACT_4394 (Reactome)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
ComplexREACT_7367 (Reactome)
p-CDC6ProteinQ99741 (Uniprot-TrEMBL)
p-FZR1 [nucleoplasm]ProteinQ9UM11 (Uniprot-TrEMBL)
p-RB1 [nucleoplasm]ProteinP06400 (Uniprot-TrEMBL) The pRB C-terminus contains a cluster of seven candidate in vivo cdk phosphorylation sites (residues 795, 807, 811, 821, and 826) and is phosphorylated in vitro by cyclin A, cyclin E, and cyclin D-associated kinases.
p-S,T-ORC1ProteinQ13415 (Uniprot-TrEMBL)
p-S130-CDKN1A [nucleoplasm]ProteinP38936 (Uniprot-TrEMBL)
p-T160-CDK2 [nucleoplasm]ProteinP24941 (Uniprot-TrEMBL)
p-T187-CDKN1B [nucleoplasm]ProteinP46527 (Uniprot-TrEMBL)
p-T286-CCND1 [cytosol]ProteinP24385 (Uniprot-TrEMBL)
p-T286-CCND1 [nucleoplasm]ProteinP24385 (Uniprot-TrEMBL)
p-T286-CCND1ProteinP24385 (Uniprot-TrEMBL)
p-Y15-CDK2 [nucleoplasm]ProteinP24941 (Uniprot-TrEMBL)
p21/p27ProteinREACT_8306 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ComplexREACT_4903 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ComplexREACT_5446 (Reactome)
pre-replicative complex (Orc1-minus)ComplexREACT_3695 (Reactome)
pre-replicative complexComplexREACT_4388 (Reactome)
ubiquitinProteinREACT_3995 (Reactome)
ubiquitinated Cdc6ComplexREACT_5308 (Reactome)
ubiquitinated Orc1ComplexREACT_5173 (Reactome)
ubiquitinated Orc1ComplexREACT_5402 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisREACT_1210 (Reactome)
26S proteasomemim-catalysisREACT_2142 (Reactome)
26S proteasomemim-catalysisREACT_480 (Reactome)
26S proteasomemim-catalysisREACT_9034 (Reactome)
ADPArrowREACT_1279 (Reactome)
ADPArrowREACT_132 (Reactome)
ADPArrowREACT_1994 (Reactome)
ADPArrowREACT_2111 (Reactome)
ADPArrowREACT_8998 (Reactome)
ADPArrowREACT_9007 (Reactome)
ADPArrowREACT_9057 (Reactome)
ADPArrowREACT_9070 (Reactome)
AMPArrowREACT_315 (Reactome)
ATPREACT_1279 (Reactome)
ATPREACT_132 (Reactome)
ATPREACT_1673 (Reactome)
ATPREACT_1994 (Reactome)
ATPREACT_2111 (Reactome)
ATPREACT_8998 (Reactome)
ATPREACT_9007 (Reactome)
ATPREACT_9057 (Reactome)
ATPREACT_9070 (Reactome)
Ac-CoAREACT_150144 (Reactome)
Ac-CoAREACT_150456 (Reactome)
Ac-Cohesin:PDS5:WAPAL:CentromereArrowREACT_150144 (Reactome)
Ac-Cohesin:PDS5:WAPAL:CentromereREACT_150445 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmArrowREACT_150456 (Reactome)
Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmREACT_150264 (Reactome)
CAKmim-catalysisREACT_9070 (Reactome)
CDC25AArrowREACT_9013 (Reactome)
CDC45REACT_6963 (Reactome)
CDC6ArrowREACT_1279 (Reactome)
CDC6REACT_1279 (Reactome)
CDC6REACT_448 (Reactome)
CDCA5REACT_150264 (Reactome)
CDCA5REACT_150445 (Reactome)
CDK2REACT_8996 (Reactome)
CDKN1AArrowREACT_9068 (Reactome)
CDKN1AREACT_9068 (Reactome)
CDKN1BArrowREACT_9043 (Reactome)
CDKN1BREACT_9043 (Reactome)
CDKmim-catalysisREACT_1279 (Reactome)
CKS1BREACT_9017 (Reactome)
CMPArrowREACT_315 (Reactome)
Cdc25 A/Bmim-catalysisREACT_9062 (Reactome)
CoA-SHArrowREACT_150144 (Reactome)
CoA-SHArrowREACT_150456 (Reactome)
Cohesin:PDS5:WAPAL:CentromereREACT_150144 (Reactome)
Cohesin:PDS5:WAPAL:Chromosomal ArmREACT_150456 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
ArrowREACT_9005 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
REACT_8995 (Reactome)
Cyclin

A:Cdk2:p21/p27

complex
mim-catalysisREACT_8995 (Reactome)
Cyclin

A:Cdk2:phospho-p27/p21

complex
ArrowREACT_8995 (Reactome)
Cyclin

A:Cdk2:phosphorylated

substrate complex
ArrowREACT_9007 (Reactome)
Cyclin

A:Cdk2:substrate

complex
REACT_9007 (Reactome)
Cyclin

A:Cdk2:substrate

complex
mim-catalysisREACT_2111 (Reactome)
Cyclin

A:Cdk2:substrate

complex
mim-catalysisREACT_9007 (Reactome)
Cyclin

A:phospho-Cdk2(Thr160)

complex
ArrowREACT_9070 (Reactome)
Cyclin

A:phospho-Cdk2(Tyr

15)
ArrowREACT_9057 (Reactome)
Cyclin

A:phospho-Cdk2(Tyr

15)
REACT_9062 (Reactome)
Cyclin

E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1

complex
ArrowREACT_9026 (Reactome)
Cyclin

E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1

complex
REACT_9034 (Reactome)
Cyclin

E/A:Cdk2:multiubiquitinated phospho-p27/p21:SCF(Skp2):Cks1

complex
mim-catalysisREACT_9026 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
REACT_8998 (Reactome)
Cyclin

E/A:Cdk2:p27/p21

complex
mim-catalysisREACT_8998 (Reactome)
Cyclin

E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1

complex
ArrowREACT_9060 (Reactome)
Cyclin

E/A:Cdk2:phospho-p27/p21:SCF(Skp2):Cks1

complex
REACT_9026 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21ArrowREACT_8998 (Reactome)
Cyclin E/A:Cdk2:phospho-p27/p21REACT_9060 (Reactome)
Cyclin A:Cdk2 complexArrowREACT_8996 (Reactome)
Cyclin A:Cdk2 complexArrowREACT_9062 (Reactome)
Cyclin A:Cdk2 complexArrowREACT_9065 (Reactome)
Cyclin A:Cdk2 complexREACT_9005 (Reactome)
Cyclin A:Cdk2 complexREACT_9057 (Reactome)
Cyclin A:Cdk2 complexREACT_9065 (Reactome)
Cyclin A:Cdk2 complexREACT_9070 (Reactome)
Cyclin AREACT_8996 (Reactome)
Cyclin D1:Cdk4REACT_132 (Reactome)
Cyclin E/A:Cdk2ArrowREACT_9034 (Reactome)
DNA Polymerase delta tetramerREACT_1009 (Reactome)
DNA Polymerase delta tetramerREACT_149 (Reactome)
DNA Polymerase delta tetramermim-catalysisREACT_1024 (Reactome)
DNA polymerase

alpha:primase:DNA polymerase

alpha:origin complex
REACT_1611 (Reactome)
DNA polymerase alpha:primasemim-catalysisREACT_1611 (Reactome)
DNA polymerase alpha:primasemim-catalysisREACT_91 (Reactome)
DNA polymerase epsilonArrowREACT_1611 (Reactome)
DNA2ArrowREACT_315 (Reactome)
DNA2REACT_1278 (Reactome)
ESCOmim-catalysisREACT_150144 (Reactome)
ESCOmim-catalysisREACT_150456 (Reactome)
FEN1mim-catalysisREACT_2024 (Reactome)
GINS complexArrowREACT_6747 (Reactome)
GINS complexREACT_6963 (Reactome)
GINS1REACT_6747 (Reactome)
GINS2REACT_6747 (Reactome)
GINS4(1-223)REACT_6747 (Reactome)
GMPArrowREACT_315 (Reactome)
H2OREACT_9062 (Reactome)
LIG1mim-catalysisREACT_1889 (Reactome)
MCM2ArrowREACT_1303 (Reactome)
MCM3ArrowREACT_1303 (Reactome)
MCM5ArrowREACT_1303 (Reactome)
MCM8mim-catalysisREACT_6768 (Reactome)
Mcm2-7 complexREACT_1303 (Reactome)
Mcm2-7 complexREACT_6963 (Reactome)
Mcm2-7 complexmim-catalysisREACT_6922 (Reactome)
Mcm4,6,7 complexArrowREACT_1303 (Reactome)
Myc/Max heterodimerArrowREACT_9013 (Reactome)
NTPREACT_1611 (Reactome)
Okazaki fragmentREACT_1889 (Reactome)
PCNA homotrimerREACT_1994 (Reactome)
PSF3pREACT_6747 (Reactome)
PiArrowREACT_9062 (Reactome)
Processive

complex:Okazaki

fragment complex
ArrowREACT_1024 (Reactome)
Processive

complex:Okazaki

fragment complex
REACT_1572 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
ArrowREACT_1278 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer:dna2
REACT_315 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
ArrowREACT_2026 (Reactome)
Processive

complex:Okazaki fragment:Flap:RPA

heterotrimer
REACT_1278 (Reactome)
Processive

complex:Okazaki

fragment:Flap
ArrowREACT_1572 (Reactome)
Processive

complex:Okazaki

fragment:Flap
REACT_2026 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
ArrowREACT_315 (Reactome)
Processive

complex:Okazaki fragments:Remaining

Flap
REACT_2024 (Reactome)
Processive

complex:nicked DNA from adjacent

Okazaki fragments
ArrowREACT_2024 (Reactome)
Processive complexArrowREACT_1009 (Reactome)
Processive complexArrowREACT_149 (Reactome)
Processive complexREACT_1024 (Reactome)
REACT_1009 (Reactome) The loading of proliferating cell nuclear antigen (PCNA) leads to recruitment of pol delta. Human PCNA is a homotrimer of 36 kDa subunits that form a toroidal structure. The loading of PCNA by RFC is a key event in the transition from the priming mode to the extension mode of DNA synthesis. The processive complex is composed of the pol delta holoenzyme and PCNA.
REACT_1024 (Reactome) After RFC initiates the assembly of the primer recognition complex, the complex of pol delta and PCNA is responsible for incorporating the additional nucleotides prior to the position of the next downstream initiator RNA primer. On the lagging strand, short discontinuous segments of DNA, called Okazaki fragments, are synthesized on RNA primers. The average length of the Okazaki fragments is 100 nucleotides. Polymerase switching is a key event that allows the processive synthesis of DNA by the pol delta and PCNA complex.
REACT_1180 (Reactome) In this reaction, 1 molecule of 'phospho(T286)-Cyclin D1' is translocated from nucleoplasm to cytosol.

This reaction takes place in the 'nuclear envelope'.

REACT_1210 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitinated Cdc6' is present. At the end of this reaction, 1 molecule of 'ubiquitin' is present.

This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of '26S proteasome'.

REACT_1278 (Reactome) After RPA binds the long flap, it recruits the Dna2 endonuclease. Dna2 endonuclease removes most of the flap, but the job of complete removal of the flap is then completed by FEN-1.
REACT_1279 (Reactome) At the beginning of this reaction, 1 molecule of 'CDC6', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ADP', and 1 molecule of 'phosphorylated Cdc6' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'CDK'.

REACT_1303 (Reactome) At the start of the elongation phase of DNA replication, the Mcm2-7 complex may re-arrange to function as the replicative helicase associated with the replication fork. In general, a replicative helicase is associated with the replication fork and unwinds DNA ahead of the polymerase. In yeast, the Mcm proteins associate with origin DNA in G1 phase and then exit the origin upon replication initiation, consistent with moving out of the origin with the replication fork. The Mcm2-7 complex is a ring-shaped hexamer. Complexes of Mcm4, Mcm6 and Mcm7 proteins from humans or S. pombe display a modest ATP-dependent helicase activity in vitro. Consistent with the hypothesis that eukaryotic Mcm complexes function as helicases, an archaeal Mcm homolog is a ring-shaped double hexamer that has a processive DNA unwinding activity. Mcm proteins may have additional functions during elongation, as uninterrupted function of all six is required for replication fork progression in budding yeast. Mcm4,6,7 helicase activity may be negatively regulated in two ways. Mcm2, Mcm4, Mcm6, and Mcm7 also form a stable complex which, however, has no helicase activity, suggesting that Mcm2 inhibits DNA unwinding by Mcm4,6,7. In addition, phosphorylation of human Mcm4,6,7 complex by CDK inhibits its helicase activity.
REACT_132 (Reactome) At the beginning of this reaction, 1 molecule of 'Cyclin D1:Cdk4', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'phospho(T286)-Cyclin D1:Cdk4', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'glycogen synthase kinase-3 beta'.

REACT_149 (Reactome) Polymerase switching is a key event that allows the processive synthesis of DNA by the pol delta and PCNA complex. Polymerase delta possesses polymerization and proofreading activities, which increases the overall fidelity of DNA replication. The pol delta holoenzyme is a heterotetrameric complex that contains p125, p66, p50, and p12 subunits, in human cells.
REACT_150144 (Reactome) Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. Divergent N-termini of ESCO1 and ESCO2, necessary for chromatin binding, suggest that ESCO1 and ESCO2 may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005). Several studies suggest that ESCO2 may be predominantly involved in acetylation of the SMC3 subunit of centromeric cohesin. A conditional targeting of Esco2 locus in mice leads to pre-implantational loss of homozygous Esco2 -/- embryos at the eight-cell stage. Prometaphase chromosomes isolated from two-cell stage Esco2 knockout embryos show marked cohesion defect at centromeres (Whelan et al. 2012). ESCO2 protein appears in the S-phase (Hou and Zou 2005, Whelan et al. 2012) and in mouse embryonic fibroblasts Esco2 predominantly localizes to pericentric heterochromatin (Whelan et al. 2012). Mutations in the ESCO2 gene (Vega et al. 2005) that impair ESCO2 acetyltransferase activity (Gordillo et al. 2008) are the cause of the Roberts syndrome, an autosomal recessive disorder characterized by craniofacial and limb abnormalities, and intellectual disability. Metaphase chromosomes of Roberts syndrome patients exhibit loss of cohesion at heterochromatic regions of centromeres and the Y chromosome, with a characteristic 'railroad track appearance' (Van den Berg and Francke 1993, Vega et al. 2005).
REACT_150264 (Reactome) CDCA5 (Sororin) is essential for the establishment of sister chromatid cohesion in mammalian cells (Rankin et al. 2005) in the S-phase of the cell cycle (Nishiyama et al. 2010). Several factors contribute to the recruitment of CDCA5 to chromatin-associated cohesin: DNA replication (i.e. presence of two sister chromatids), association of cohesin complex with PDS5, and acetylation of the SMC3 cohesin subunit by ESCO1/ESCO2 acetyltransferases. Experiments in which a recombinant tagged mouse CDCA5 was expressed in human HeLa cell line showed that CDCA5 starts to accumulate on chromatin in S-phase and dissociates from chromosomal arms in prophase (Nishiyama et al. 2010).

CDCA5 is essential for the establishment of chromosomal cohesion only in the presence of WAPAL, suggesting that the key role of CDCA5 (Sororin) is to antagonize WAPAL. Both CDCA5 and WAPAL contain an FGF (phenylalanine-glycine-phenylalanine) motif that is essential for PDS5 binding and is also essential for CDCA5 function in cohesion establishment. Indeed, CDCA5 is able to displace WAPAL from PDS5:WAPAL heterodimers in vitro. In vivo experiments in Xenopus egg extracts suggest that CDCA5 rearranges the topology of cohesin associated proteins so that WAPAL is no longer able to inhibit sister chromatid cohesion but remains associated with cohesin (Nishiyama et al. 2010).
REACT_150445 (Reactome) CDCA5 (Sororin) is essential for the establishment of sister chromatid cohesion at centromeres. Experiments in which a recombinant tagged mouse CDCA5 was expressed in human HeLa cell line showed that CDCA5 starts to accumulate on chromatin in S-phase and dissociates from centromeres in anaphase (Nishiyama et al. 2010).
REACT_150456 (Reactome) Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. These dual acetylations on SMC3 are deacetylated by HDAC8 after the cohesin removal from chromatin for the dissociation and recycling of cohesin subunits (Deardorff et al. 2012). ESCO1 and ESCO2 differ in their N-termini, which are necessary for chromatin binding, and may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005), as suggested by the study of Esco2 knockout mice (Whelan et al. 2012).
REACT_1572 (Reactome) When the polymerase delta:PCNA complex reaches a downstream Okazaki fragment, strand displacement synthesis occurs. The primer containing 5'-terminus of the downstream Okazaki fragment is folded into a single-stranded flap.
REACT_1611 (Reactome) At the beginning of this reaction, 1 molecule of 'DNA polymerase alpha:primase:DNA polymerase alpha:origin complex', and 1 molecule of 'NTP' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:primase complex' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed RNA polymerase activity' of 'DNA polymerase alpha:primase'.

REACT_1626 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitin', and 1 molecule of 'phosphorylated Orc1' are present. At the end of this reaction, 1 molecule of 'ubiquitinated Orc1' is present.

This reaction takes place in the 'nucleus'.

REACT_1673 (Reactome) At the beginning of this reaction, 1 molecule of 'phosphorylated Cdc6', 1 molecule of 'ubiquitin', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ubiquitinated Cdc6' is present.

This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of 'anaphase-promoting complex (APC)'.

REACT_1871 (Reactome) Once the RNA-DNA primer is synthesized, replication factor C (RFC) initiates a reaction called "polymerase switching"; pol delta, the processive enzyme replaces pol alpha, the priming enzyme. RFC binds to the 3'-end of the RNA-DNA primer on the Primosome, to displace the pol alpha primase complex. The binding of RFC triggers the binding of the primer recognition complex.
REACT_1889 (Reactome) Removal of the flap by FEN-1 leads to the generation of a nick between the 3'-end of the upstream Okazaki fragment and the 5'-end of the downstream Okazaki fragment. DNA ligase I then seals the nicks between adjacent processed Okazaki fragments to generate intact double-stranded DNA.
REACT_1994 (Reactome) The binding of the primer recognition complex involves the loading of proliferating cell nuclear antigen (PCNA). Replication Factor C transiently opens the PCNA toroid in an ATP-dependent reaction, and then allows PCNA to re-close around the double helix adjacent to the primer terminus. This leads to the formation of the "sliding clamp".
REACT_2024 (Reactome) The remaining flap, which is too short to support RPA binding, is then processed by FEN-1. There is evidence that binding of RPA to the displaced end of the RNA-containing Okazaki fragment prevents FEN-1 from accessing the substrate. FEN-1 is a structure-specific endonuclease that cleaves near the base of the flap at a position one nucleotide into the annealed region. Biochemical studies have shown that the preferred substrate for FEN-1 consists of a one-nucleotide 3'-tail on the upstream primer in addition to the 5'-flap of the downstream primer.
REACT_2026 (Reactome) The first step in the removal of the flap intermediate is the binding of Replication Protein A (RPA) to the long flap structure. RPA is a eukaryotic single-stranded DNA binding protein.
REACT_210 (Reactome) In this reaction, 1 molecule of 'ubiquitinated Orc1' is translocated from nucleoplasm to cytosol.

This movement of the molecule occurs through the 'nuclear pore'.

REACT_2111 (Reactome) At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'pre-replicative complex' are present. At the end of this reaction, 1 molecule of 'phosphorylated Orc1', 1 molecule of 'pre-replicative complex (Orc1-minus)', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'Cyclin A:Cdk2 complex'.

REACT_2142 (Reactome) Phosphorylated Cyclin D1 is degraded during S phase by the 26S proteasome allowing for efficient DNA synthesis.
REACT_315 (Reactome) The Dna2 endonuclease removes the initiator RNA along with several downstream deoxyribonucleotides. The cleavage of the single-stranded RNA substrate results in the disassembly of RPA and Dna2. The current data for the role of the Dna2 endonuclease has been derived from studies with yeast and Xenopus Dna2.
REACT_351 (Reactome) Replication factor C is proposed to dissociate from PCNA following sliding clamp formation, and the DNA toroid alone tethers pol delta to the DNA.
REACT_448 (Reactome) In this reaction, 1 molecule of 'phosphorylated Cdc6' is translocated from nucleoplasm to cytosol.

This movement of the molecule occurs through the 'nuclear pore'.

REACT_480 (Reactome) At the beginning of this reaction, 1 molecule of 'ubiquitinated Orc1' is present. At the end of this reaction, 1 molecule of 'ubiquitin' is present.

This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of '26S proteasome'.

REACT_6747 (Reactome) At the beginning of this reaction, 1 molecule of 'PSF3p', 1 molecule of 'SLD5P', 1 molecule of 'PSF2p', and 1 molecule of 'PSF1p' are present. At the end of this reaction, 1 molecule of 'GINS complex' is present.

This reaction takes place in the 'nucleus'.

REACT_6768 (Reactome) The MCM2-7 related protein, MCM8, is required to replicate chromosomal DNA in Xenopus egg extracts. MCM8 binds chromatin upon initiation of DNA synthesis. It may function as an helicase in the elongation step.
REACT_6922 (Reactome) In budding yeast, all MCM proteins have been proved to be essential for elongation. The active form of this protein complex may be a heterohexamer. A subcomplex of MCM proteins consisting fo MCM4,6, and -7 has a weak helicase activity that may contribute to DNA unwinding.
REACT_6963 (Reactome) By applying the chromatin immunoprecipitation technique to paused forks, certain proteins like DNA pol alpha, DNA pol delta, DNA pol epsilon, MCM2-7, CDC45, GINS and MCM10 were identified. By uncoupling a helicase at the site using a polymerase inhibitor, MCM2-7, GINS complex and CDC45 alone were found to be enriched at the paused fork suggesting these proteins may form a part of an "unwindosome" at the replicating fork.
REACT_715 (Reactome) Cyclin D is targeted for degradation by multi-ubiquitination.
REACT_752 (Reactome) In this reaction, 1 molecule of 'phospho(T286)-Cyclin D1:Cdk4' is translocated from nucleoplasm to cytosol.

This reaction takes place in the 'nuclear envelope'.

REACT_8995 (Reactome) Recognition of p27 by SCF(Skp2) and the subsequent ubiquitination of p27 is dependent upon Cyclin E/A:Cdk2-mediated phosphorylation of p27 at Thr 187 (Montagnoli et al., 1999). p21 is also phosphorylated at a specific site (Ser130) by Cyclin E/A:Cdk2, stimulating its ubiquitination. Unlike p27, however, p21 ubiquitination can take place in the absence of phosphorylation, although with less efficiency (Bornstein et al.,2003).
REACT_8996 (Reactome) During G1 phase of the cell cycle, cyclin A is synthesized and associates with Cdk2.
REACT_8998 (Reactome) The interaction between the Skp2 subunit of the SCF(Skp2) complex and p27 is dependent upon Cdk2:Cyclin A/E mediated phosphorylation of p27 at Thr 187 (Carrano et al, 1999; Tsvetkov et al, 1999). There is evidence that Cyclin A/B:Cdk1 can also bind and phosphorylate p27 on Thr 187 (Nakayama et al., 2004). This phosphorylation is also essential for the subsequent ubiquitination of p27.
REACT_9005 (Reactome) During G1, the activity of cyclin-dependent kinases (CDKs) is kept in check by the CDK inhibitors (CKIs) p27 and p21, thereby preventing premature entry into S phase (see Guardavaccaro and Pagano, 2006).
REACT_9007 (Reactome) Active Cyclin A:Cdk2 complexes phosphorylate and inactivate proteins required for maintaining the G1/S phase including: Cdh1, RB1, p21 and p27. All this creates auto-amplification loops that render Cdk2 increasingly more active. In G2, Cdk2, in association with cyclin A, phosphorylates E2F1 and E2F3 resulting in the inactivation and possibly degradation of these two transcription factors (Dynlacht et al., 1994; Krek et al., 1994).
REACT_9013 (Reactome) The Myc/Max heterodimer binds to elements in the cdc25A gene and activates transcription in mid to late G1.
REACT_9017 (Reactome) The accessory protein, Cks1 promotes efficient interaction between phosphorylated p27 and the SCF (Skp2) complex (Ganoth et al., 2001; Spruck et al., 2001). Cks1 binds to Skp2 in the leucine-rich repeat (LRR) domain and C-terminal tail (Hao et al., 2005). The phosphorylated Thr187 side chain of p27 associates with a phosphate binding site on Cks1, and the side chain containing Glu185 is positioned in the interface between Skp2 and Cks1 where it interacts with both (Hao et al., 2005).
REACT_9026 (Reactome) Once in tight contact with the SCF (Skp2):Cks1 complex, phosphorylated p27/p21 is ubiquitinated.
REACT_9034 (Reactome) Following ubiquitination by the SCF(Skp2):Cks1 complex, phospho-p27/p21 is degraded by the 26S proteasome.
REACT_9043 (Reactome) p27 translocates to the nucleoplasm where it associates with CyclinE:Cdk2 complexes. Localization of p27 to the nucleus is necessary to inhibit Cdk activation by Cdk-activating kinase.
REACT_9057 (Reactome) The CDK activity of the Cyclin A:Cdk2 complex is inhibited by phosphorylation at Tyr 15, presumably by the Wee1 kinase.
REACT_9060 (Reactome) The association of Cks1 with both Skp2 and phosphorylated p27 promotes a tight interaction between p27 and the SCF complex (Hao et al., 2005).
REACT_9062 (Reactome) Cdc25A, and probably Cdc25B, regulate the entry into S phase cell cycle by removing inhibitory phosphates from the Cdk2 subunit of Cyclin A:Cdk2.
REACT_9065 (Reactome) After forming in the cytoplasm, the Cyclin A:Cdk2 complexes are translocated to the nucleus.
REACT_9068 (Reactome) p21 associates with and inhibits Cyclin:Cdk complexes in the nucleus.
REACT_9070 (Reactome) Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase (CAK) is required for the activation of the CDK kinase activity. The association of p21/p27 with the Cyclin A/E:Cdk2 complex prevents CAK mediated phosphorylation of Cdk2 (Aprelikova et al., 1995).
REACT_91 (Reactome) At the beginning of this reaction, 1 molecule of 'dTTP', 1 molecule of 'dGTP', 1 molecule of 'dATP', 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:primase complex', and 1 molecule of 'dCTP' are present. At the end of this reaction, 1 molecule of 'RNA primer-DNA primer:origin duplex' is present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase alpha:primase'.

RFC

Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA

homotrimer
ArrowREACT_1994 (Reactome)
RFC

Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA

homotrimer
REACT_351 (Reactome)
RFC

Heteropentamer:RNA primer-DNA

primer:origin duplex
ArrowREACT_1871 (Reactome)
RFC

Heteropentamer:RNA primer-DNA

primer:origin duplex
REACT_1994 (Reactome)
RFC HeteropentamerArrowREACT_351 (Reactome)
RFC HeteropentamerREACT_1871 (Reactome)
RNA primer-DNA

primer:origin

duplex:PCNA
ArrowREACT_351 (Reactome)
RNA primer-DNA

primer:origin

duplex:PCNA
REACT_1009 (Reactome)
RNA primer-DNA

primer:origin

duplex:PCNA
REACT_149 (Reactome)
RNA primer-DNA primer:origin duplexArrowREACT_91 (Reactome)
RNA primer-DNA primer:origin duplexREACT_1871 (Reactome)
RNA primer:origin

duplex:DNA polymerase alpha:primase

complex
ArrowREACT_1611 (Reactome)
RNA primer:origin

duplex:DNA polymerase alpha:primase

complex
REACT_91 (Reactome)
RPA heterotrimerArrowREACT_315 (Reactome)
RPA heterotrimerREACT_2026 (Reactome)
Replication ForkREACT_6768 (Reactome)
Replication ForkREACT_6922 (Reactome)
Replication ForkREACT_6963 (Reactome)
SCF(Skp2) complexREACT_9017 (Reactome)
SCF(Skp2):Cks1 complexArrowREACT_9017 (Reactome)
SCF(Skp2):Cks1 complexArrowREACT_9034 (Reactome)
SCF(Skp2):Cks1 complexREACT_9060 (Reactome)
Sister Centromeres:Ac-Cohesin:PDS5:CDCA5:WAPALArrowREACT_150445 (Reactome)
Sister CentromereREACT_150445 (Reactome)
Sister Chromosomal ArmREACT_150264 (Reactome)
Sister Chromosomal Arms:Ac-Cohesin:PDS5:CDCA5:WAPALArrowREACT_150264 (Reactome)
UMPArrowREACT_315 (Reactome)
UbArrowREACT_1210 (Reactome)
UbArrowREACT_2142 (Reactome)
UbArrowREACT_480 (Reactome)
UbREACT_1673 (Reactome)
UbREACT_715 (Reactome)
Ubiquitin ligasemim-catalysisREACT_715 (Reactome)
Unwinding complex at replication forkArrowREACT_6963 (Reactome)
Unwound forkArrowREACT_6768 (Reactome)
Unwound forkArrowREACT_6922 (Reactome)
WEE1mim-catalysisREACT_9057 (Reactome)
anaphase-promoting complex (APC)mim-catalysisREACT_1673 (Reactome)
dATPREACT_91 (Reactome)
dCTPREACT_91 (Reactome)
dGTPREACT_91 (Reactome)
dTTPREACT_91 (Reactome)
glycogen synthase kinase-3 betamim-catalysisREACT_132 (Reactome)
ligated okazaki fragmentArrowREACT_1889 (Reactome)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
ArrowREACT_715 (Reactome)
multi-ubiquitinated

phospho-(T286)

Cyclin D1
REACT_2142 (Reactome)
p-CDC6ArrowREACT_448 (Reactome)
p-CDC6REACT_1673 (Reactome)
p-S,T-ORC1ArrowREACT_2111 (Reactome)
p-S,T-ORC1REACT_1626 (Reactome)
p-T286-CCND1ArrowREACT_1180 (Reactome)
p-T286-CCND1REACT_1180 (Reactome)
p-T286-CCND1REACT_715 (Reactome)
p21/p27REACT_9005 (Reactome)
p21/p27mim-catalysisREACT_9005 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ArrowREACT_132 (Reactome)
phospho(T286)-Cyclin D1:Cdk4ArrowREACT_752 (Reactome)
phospho(T286)-Cyclin D1:Cdk4REACT_752 (Reactome)
pre-replicative complex (Orc1-minus)ArrowREACT_2111 (Reactome)
pre-replicative complexREACT_2111 (Reactome)
ubiquitinArrowREACT_9034 (Reactome)
ubiquitinREACT_1626 (Reactome)
ubiquitinREACT_9026 (Reactome)
ubiquitinated Cdc6ArrowREACT_1673 (Reactome)
ubiquitinated Cdc6REACT_1210 (Reactome)
ubiquitinated Orc1ArrowREACT_1626 (Reactome)
ubiquitinated Orc1ArrowREACT_210 (Reactome)
ubiquitinated Orc1REACT_210 (Reactome)
ubiquitinated Orc1REACT_480 (Reactome)
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