S Phase (Homo sapiens)
From WikiPathways
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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Ontology Terms
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- Diehl JA, Sherr CJ.; ''A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase.''; PubMed Europe PMC Scholia
- Nishiyama T, Ladurner R, Schmitz J, Kreidl E, Kreidl E, Schleiffer A, Bhaskara V, Bando M, Shirahige K, Hyman AA, Mechtler K, Peters JM.; ''Sororin mediates sister chromatid cohesion by antagonizing Wapl.''; PubMed Europe PMC Scholia
- Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, van Gosliga D, Kayserili H, Xu C, Ozono K, Jabs EW, Inui K, Joenje H.; ''Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion.''; PubMed Europe PMC Scholia
- Litovchick L, Sadasivam S, Florens L, Zhu X, Swanson SK, Velmurugan S, Chen R, Washburn MP, Liu XS, DeCaprio JA.; ''Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.''; PubMed Europe PMC Scholia
- 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
- Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
- 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
- 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
- Gu Y, Rosenblatt J, Morgan DO.; ''Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.''; PubMed Europe PMC Scholia
- 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
- 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
- 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
- Orend G, Hunter T, Ruoslahti E.; ''Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells.''; PubMed Europe PMC Scholia
- Van Den Berg DJ, Francke U.; ''Roberts syndrome: a review of 100 cases and a new rating system for severity.''; PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
- 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
- Bembenek J, Yu H.; ''Regulation of the anaphase-promoting complex by the dual specificity phosphatase human Cdc14a.''; PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A.; ''Noncatalytic requirement for cyclin A-cdk2 in p27 turnover.''; PubMed Europe PMC Scholia
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Hou F, Zou H.; ''Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion.''; PubMed Europe PMC Scholia
- 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
- Carrano AC, Eytan E, Hershko A, Pagano M.; ''SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.''; PubMed Europe PMC Scholia
- 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
- Galaktionov K, Chen X, Beach D.; ''Cdc25 cell-cycle phosphatase as a target of c-myc.''; PubMed Europe PMC Scholia
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| 26S proteasome | Complex | REACT_2353 (Reactome)  | |
| 26S proteasome | Complex | REACT_7467 (Reactome) | |
| 2xAcK-SMC3 | Protein | Q9UQE7 (Uniprot-TrEMBL) | |
| ADP | Metabolite | CHEBI:16761 (ChEBI) | |
| AMP | Metabolite | CHEBI:16027 (ChEBI) | |
| ATP | Metabolite | CHEBI:15422 (ChEBI) | |
| Ac-CoA | Metabolite | CHEBI:15351 (ChEBI) | |
| Ac-Cohesin
PDS5 WAPAL Centromere | Complex | REACT_152186 (Reactome) | |
| Ac-Cohesin
PDS5 WAPAL Chromosomal Arm | Complex | REACT_151929 (Reactome) | |
| CAK | Complex | REACT_5717 (Reactome) | |
| CCND1 | Protein | P24385 (Uniprot-TrEMBL) | |
| CCNH | Protein | P51946 (Uniprot-TrEMBL) | |
| CDC25A | Protein | P30304 (Uniprot-TrEMBL) | |
| CDC45 | Protein | O75419 (Uniprot-TrEMBL) | |
| CDC45 | Protein | O75419 (Uniprot-TrEMBL) | |
| CDC6 | Protein | Q99741 (Uniprot-TrEMBL) | |
| CDC6 | Protein | Q99741 (Uniprot-TrEMBL) | |
| CDCA5 | Protein | Q96FF9 (Uniprot-TrEMBL) | |
| CDCA5 | Protein | Q96FF9 (Uniprot-TrEMBL) | |
| CDK2 | Protein | P24941 (Uniprot-TrEMBL) | |
| CDK2 | Protein | P24941 (Uniprot-TrEMBL) | |
| CDK4 | Protein | P11802 (Uniprot-TrEMBL) | |
| CDK7 | Protein | P50613 (Uniprot-TrEMBL) | |
| CDKN1A | Protein | P38936 (Uniprot-TrEMBL) | |
| CDKN1A | Protein | P38936 (Uniprot-TrEMBL) | |
| CDKN1B | Protein | P46527 (Uniprot-TrEMBL) | |
| CDKN1B | Protein | P46527 (Uniprot-TrEMBL) | |
| CDK | Complex | REACT_5476 (Reactome) | |
| CDT1 | Protein | Q9H211 (Uniprot-TrEMBL) | |
| CKS1B | Protein | P61024 (Uniprot-TrEMBL) | |
| CKS1B | Protein | P61024 (Uniprot-TrEMBL) | |
| CMP | Metabolite | CHEBI:17361 (ChEBI) | |
| CUL1 | Protein | Q13616 (Uniprot-TrEMBL) | |
| Cdc25 A/B | REACT_9277 (Reactome) | ||
| CoA-SH | Metabolite | CHEBI:15346 (ChEBI) | |
| Cohesin
PDS5 WAPAL Centromere | Complex | REACT_151885 (Reactome) | |
| Cohesin
PDS5 WAPAL Chromosomal Arm | Complex | REACT_150643 (Reactome) | |
| Cyclin A
Cdk2 p21/p27 complex | Complex | REACT_9335 (Reactome) | |
| Cyclin A
Cdk2 phospho-p27/p21 complex | Complex | REACT_9145 (Reactome) | |
| Cyclin A
Cdk2 phosphorylated substrate complex | Complex | REACT_9299 (Reactome) | |
| Cyclin A
Cdk2 substrate complex | Complex | REACT_9192 (Reactome) | |
| Cyclin A Cdk2 complex | Complex | REACT_4932 (Reactome) | |
| Cyclin A Cdk2 complex | Complex | REACT_9350 (Reactome) | |
| Cyclin A phospho-Cdk2 | Complex | REACT_9202 (Reactome) | |
| Cyclin A phospho-Cdk2 | Complex | REACT_9292 (Reactome) | |
| Cyclin A | Protein | REACT_6541 (Reactome) | |
| Cyclin D1 Cdk4 | Complex | REACT_2478 (Reactome) | |
| Cyclin E/A
Cdk2 multiubiquitinated phospho-p27/p21 SCF | Complex | REACT_9266 (Reactome) | |
| Cyclin E/A
Cdk2 p27/p21 complex | Complex | REACT_9314 (Reactome) | |
| Cyclin E/A
Cdk2 phospho-p27/p21 SCF | Complex | REACT_9193 (Reactome) | |
| Cyclin E/A
Cdk2 phospho-p27/p21 | Complex | REACT_9321 (Reactome) | |
| Cyclin E/A Cdk2 | Complex | REACT_9091 (Reactome) | |
| DNA Polymerase delta tetramer | Complex | REACT_5801 (Reactome) | |
| DNA polymerase alpha
primase DNA polymerase alpha origin complex | Complex | REACT_3167 (Reactome) | |
| DNA polymerase alpha primase | Complex | REACT_3725 (Reactome) | |
| DNA polymerase epsilon | Complex | REACT_4621 (Reactome) | |
| DNA2 | Protein | P51530 (Uniprot-TrEMBL) | |
| DNA2 | Protein | P51530 (Uniprot-TrEMBL) | |
| ESCO | Protein | REACT_151079 (Reactome) | |
| FEN1 | Protein | P39748 (Uniprot-TrEMBL) | |
| FZR1 | Protein | Q9UM11 (Uniprot-TrEMBL) | |
| GINS complex | Complex | REACT_7704 (Reactome) | |
| GINS1 | Protein | Q14691 (Uniprot-TrEMBL) | |
| GINS1 | Protein | Q14691 (Uniprot-TrEMBL) | |
| GINS2 | Protein | Q9Y248 (Uniprot-TrEMBL) | |
| GINS2 | Protein | Q9Y248 (Uniprot-TrEMBL) | |
| GINS4 | Protein | Q9BRT9 (Uniprot-TrEMBL) | |
| GMP | Metabolite | CHEBI:17345 (ChEBI) | |
| H2O | Metabolite | CHEBI:15377 (ChEBI) | |
| LIG1 | Protein | P18858 (Uniprot-TrEMBL) | |
| MAX | Protein | P61244 (Uniprot-TrEMBL) | |
| MCM2 | Protein | P49736 (Uniprot-TrEMBL) | |
| MCM2 | Protein | P49736 (Uniprot-TrEMBL) | |
| MCM3 | Protein | P25205 (Uniprot-TrEMBL) | |
| MCM3 | Protein | P25205 (Uniprot-TrEMBL) | |
| MCM4 | Protein | P33991 (Uniprot-TrEMBL) | |
| MCM5 | Protein | P33992 (Uniprot-TrEMBL) | |
| MCM5 | Protein | P33992 (Uniprot-TrEMBL) | |
| MCM6 | Protein | Q14566 (Uniprot-TrEMBL) | |
| MCM7 | Protein | P33993 (Uniprot-TrEMBL) | |
| MCM8 | Protein | Q9UJA3 (Uniprot-TrEMBL) | |
| MCM8 | Protein | Q9UJA3 (Uniprot-TrEMBL) | |
| MNAT1 | Protein | P51948 (Uniprot-TrEMBL) | |
| MYC | Protein | P01106 (Uniprot-TrEMBL) | |
| Mcm2-7 complex | Complex | REACT_4763 (Reactome) | |
| Mcm4,6,7 complex | Complex | REACT_3276 (Reactome) | |
| Mitotic Prometaphase | Pathway | REACT_682 (Reactome) | 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. |
| Mitotic Telophase/Cytokinesis | Pathway | REACT_1932 (Reactome) | 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. |
| Myc/Max heterodimer | Complex | REACT_9233 (Reactome) | |
| NTP | Metabolite | REACT_4491 (Reactome) | |
| ORC1 | Protein | Q13415 (Uniprot-TrEMBL) | |
| ORC2 | Protein | Q13416 (Uniprot-TrEMBL) | |
| ORC3 | Protein | Q9UBD5 (Uniprot-TrEMBL) | |
| ORC4 | Protein | O43929 (Uniprot-TrEMBL) | |
| ORC5 | Protein | O43913 (Uniprot-TrEMBL) | |
| ORC6 | Protein | Q9Y5N6 (Uniprot-TrEMBL) | |
| Okazaki fragment | REACT_4386 (Reactome) | ||
| PCNA | Protein | P12004 (Uniprot-TrEMBL) | |
| PCNA homotrimer | Complex | REACT_2542 (Reactome) | |
| PDS5A | Protein | Q29RF7 (Uniprot-TrEMBL) | |
| PDS5B | Protein | Q9NTI5 (Uniprot-TrEMBL) | |
| POLA1 | Protein | P09884 (Uniprot-TrEMBL) | |
| POLA2 | Protein | Q14181 (Uniprot-TrEMBL) | |
| POLD1 | Protein | P28340 (Uniprot-TrEMBL) | |
| POLD2 | Protein | P49005 (Uniprot-TrEMBL) | |
| POLD3 | Protein | Q15054 (Uniprot-TrEMBL) | |
| POLD4 | Protein | Q9HCU8 (Uniprot-TrEMBL) | |
| POLE | Protein | Q07864 (Uniprot-TrEMBL) | |
| POLE2 | Protein | P56282 (Uniprot-TrEMBL) | |
| PRIM1 | Protein | P49642 (Uniprot-TrEMBL) | |
| PRIM2 | Protein | P49643 (Uniprot-TrEMBL) | |
| PSF3p | REACT_7682 (Reactome) | ||
| PSMA1 | Protein | P25786 (Uniprot-TrEMBL) | |
| PSMA2 | Protein | P25787 (Uniprot-TrEMBL) | |
| PSMA3 | Protein | P25788 (Uniprot-TrEMBL) | |
| PSMA4 | Protein | P25789 (Uniprot-TrEMBL) | |
| PSMA5 | Protein | P28066 (Uniprot-TrEMBL) | |
| PSMA6 | Protein | P60900 (Uniprot-TrEMBL) | |
| PSMA7 | Protein | O14818 (Uniprot-TrEMBL) | |
| PSMA8 | Protein | Q8TAA3 (Uniprot-TrEMBL) | |
| PSMB1 | Protein | P20618 (Uniprot-TrEMBL) | |
| PSMB10 | Protein | P40306 (Uniprot-TrEMBL) | |
| PSMB11 | Protein | A5LHX3 (Uniprot-TrEMBL) | |
| PSMB2 | Protein | P49721 (Uniprot-TrEMBL) | |
| PSMB3 | Protein | P49720 (Uniprot-TrEMBL) | |
| PSMB4 | Protein | P28070 (Uniprot-TrEMBL) | |
| PSMB5 | Protein | P28074 (Uniprot-TrEMBL) | |
| PSMB6 | Protein | P28072 (Uniprot-TrEMBL) | |
| PSMB7 | Protein | Q99436 (Uniprot-TrEMBL) | |
| PSMB8 | Protein | P28062 (Uniprot-TrEMBL) | |
| PSMB9 | Protein | P28065 (Uniprot-TrEMBL) | |
| PSMC1 | Protein | P62191 (Uniprot-TrEMBL) | |
| PSMC2 | Protein | P35998 (Uniprot-TrEMBL) | |
| PSMC3 | Protein | P17980 (Uniprot-TrEMBL) | |
| PSMC4 | Protein | P43686 (Uniprot-TrEMBL) | |
| PSMC5 | Protein | P62195 (Uniprot-TrEMBL) | |
| PSMC6 | Protein | P62333 (Uniprot-TrEMBL) | |
| PSMD1 | Protein | Q99460 (Uniprot-TrEMBL) | |
| PSMD10 | Protein | O75832 (Uniprot-TrEMBL) | |
| PSMD11 | Protein | O00231 (Uniprot-TrEMBL) | |
| PSMD12 | Protein | O00232 (Uniprot-TrEMBL) | |
| PSMD13 | Protein | Q9UNM6 (Uniprot-TrEMBL) | |
| PSMD14 | Protein | O00487 (Uniprot-TrEMBL) | |
| PSMD2 | Protein | Q13200 (Uniprot-TrEMBL) | |
| PSMD3 | Protein | O43242 (Uniprot-TrEMBL) | |
| PSMD4 | Protein | P55036 (Uniprot-TrEMBL) | |
| PSMD5 | Protein | Q16401 (Uniprot-TrEMBL) | |
| PSMD6 | Protein | Q15008 (Uniprot-TrEMBL) | |
| PSMD7 | Protein | P51665 (Uniprot-TrEMBL) | |
| PSMD8 | Protein | P48556 (Uniprot-TrEMBL) | |
| PSMD9 | Protein | O00233 (Uniprot-TrEMBL) | |
| PSME1 | Protein | Q06323 (Uniprot-TrEMBL) | |
| PSME2 | Protein | Q9UL46 (Uniprot-TrEMBL) | |
| PSME3 | Protein | P61289 (Uniprot-TrEMBL) | |
| PSME4 | Protein | Q14997 (Uniprot-TrEMBL) | |
| PSMF1 | Protein | Q92530 (Uniprot-TrEMBL) | |
| Pi | Metabolite | CHEBI:18367 (ChEBI) | |
| Processive complex
Okazaki fragment Flap RPA heterotrimer dna2 | Complex | REACT_3597 (Reactome) | |
| Processive complex
Okazaki fragment Flap RPA heterotrimer | Complex | REACT_4699 (Reactome) | |
| Processive complex
Okazaki fragment Flap | Complex | REACT_4984 (Reactome) | |
| Processive complex Okazaki fragment complex | Complex | REACT_5537 (Reactome) | |
| Processive complex
Okazaki fragments Remaining Flap | Complex | REACT_4338 (Reactome) | |
| Processive complex nicked DNA from adjacent Okazaki fragments | Complex | REACT_4371 (Reactome) | |
| Processive complex | Complex | REACT_3120 (Reactome) | |
| RAD21 | Protein | O60216 (Uniprot-TrEMBL) | |
| RB1 | Protein | P06400 (Uniprot-TrEMBL) | |
| RFC Heteropentamer
RNA primer-DNA primer origin duplex PCNA homotrimer | Complex | REACT_5474 (Reactome) | |
| RFC Heteropentamer
RNA primer-DNA primer origin duplex | Complex | REACT_5241 (Reactome) | |
| RFC Heteropentamer | Complex | REACT_4881 (Reactome) | |
| RFC1 | Protein | P35251 (Uniprot-TrEMBL) | |
| RFC2 | Protein | P35250 (Uniprot-TrEMBL) | |
| RFC3 | Protein | P40938 (Uniprot-TrEMBL) | |
| RFC4 | Protein | P35249 (Uniprot-TrEMBL) | |
| RFC5 | Protein | P40937 (Uniprot-TrEMBL) | |
| RNA primer
origin duplex DNA polymerase alpha primase complex | Complex | REACT_5709 (Reactome) | |
| RNA primer-DNA primer
origin duplex PCNA | Complex | REACT_4810 (Reactome) | |
| RNA primer-DNA primer origin duplex | Complex | REACT_5497 (Reactome) | |
| RPA heterotrimer | Complex | REACT_3427 (Reactome) | |
| RPA1 | Protein | P27694 (Uniprot-TrEMBL) | |
| RPA2 | Protein | P15927 (Uniprot-TrEMBL) | |
| RPA3 | Protein | P35244 (Uniprot-TrEMBL) | |
| RPS27A | Protein | P62979 (Uniprot-TrEMBL) | |
| Replication Fork | REACT_7812 (Reactome) | ||
| SCF | Complex | REACT_9182 (Reactome) | |
| SCF | Complex | REACT_9339 (Reactome) | |
| SKP1 | Protein | P63208 (Uniprot-TrEMBL) | |
| SKP2 | Protein | Q13309 (Uniprot-TrEMBL) | |
| SMC1A | Protein | Q14683 (Uniprot-TrEMBL) | |
| SMC3 | Protein | Q9UQE7 (Uniprot-TrEMBL) | |
| STAG1 | Protein | Q8WVM7 (Uniprot-TrEMBL) | |
| STAG2 | Protein | Q8N3U4 (Uniprot-TrEMBL) | |
| Sister Centromere | REACT_151483 (Reactome) | ||
| Sister Centromeres
Ac-Cohesin PDS5 CDCA5 WAPAL | Complex | REACT_151874 (Reactome) | |
| Sister Chromosomal Arm | REACT_150847 (Reactome) | ||
| Sister Chromosomal Arms
Ac-Cohesin PDS5 CDCA5 WAPAL | Complex | REACT_150576 (Reactome) | |
| UBA52 | Protein | P62987 (Uniprot-TrEMBL) | |
| UBB | Protein | P0CG47 (Uniprot-TrEMBL) | |
| UBC | Protein | P0CG48 (Uniprot-TrEMBL) | |
| UMP | Metabolite | CHEBI:16695 (ChEBI) | |
| Ub | Protein | REACT_3316 (Reactome) | |
| Ubiquitin ligase | REACT_4282 (Reactome) | ||
| Unwinding complex at replication fork | Complex | REACT_7007 (Reactome) | |
| Unwound fork | REACT_7610 (Reactome) | ||
| WAPAL | Protein | Q7Z5K2 (Uniprot-TrEMBL) | |
| WEE1 | Protein | P30291 (Uniprot-TrEMBL) | |
| anaphase-promoting complex | REACT_3388 (Reactome) | ||
| dATP | Metabolite | CHEBI:16284 (ChEBI) | |
| dCTP | Metabolite | CHEBI:16311 (ChEBI) | |
| dGTP | Metabolite | CHEBI:16497 (ChEBI) | |
| dTTP | Metabolite | CHEBI:18077 (ChEBI) | |
| glycogen synthase kinase-3 beta | REACT_3846 (Reactome) | ||
| ligated okazaki fragment | REACT_4394 (Reactome) | ||
| multi-ubiquitinated phospho- | Complex | REACT_7367 (Reactome) | |
| p-CDC6 | Protein | Q99741 (Uniprot-TrEMBL) | |
| p-FZR1 | Protein | Q9UM11 (Uniprot-TrEMBL) | |
| p-RB1 | Protein | P06400 (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-ORC1 | Protein | Q13415 (Uniprot-TrEMBL) | |
| p-S130-CDKN1A | Protein | P38936 (Uniprot-TrEMBL) | |
| p-T160-CDK2 | Protein | P24941 (Uniprot-TrEMBL) | |
| p-T187-CDKN1B | Protein | P46527 (Uniprot-TrEMBL) | |
| p-T286-CCND1 | Protein | P24385 (Uniprot-TrEMBL) | |
| p-T286-CCND1 | Protein | P24385 (Uniprot-TrEMBL) | |
| p-Y15-CDK2 | Protein | P24941 (Uniprot-TrEMBL) | |
| p21/p27 | Protein | REACT_8306 (Reactome) | |
| phospho | Complex | REACT_4903 (Reactome) | |
| phospho | Complex | REACT_5446 (Reactome) | |
| pre-replicative complex | Complex | REACT_3695 (Reactome) | |
| pre-replicative complex | Complex | REACT_4388 (Reactome) | |
| ubiquitin | Protein | REACT_3995 (Reactome) | |
| ubiquitinated Cdc6 | Complex | REACT_5308 (Reactome) | |
| ubiquitinated Orc1 | Complex | REACT_5173 (Reactome) | |
| ubiquitinated Orc1 | Complex | REACT_5402 (Reactome) |
Annotated Interactions
| View all... |
| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 26S proteasome | mim-catalysis | REACT_1210 (Reactome) | ||
| 26S proteasome | mim-catalysis | REACT_2142 (Reactome) | ||
| 26S proteasome | mim-catalysis | REACT_480 (Reactome) | ||
| 26S proteasome | mim-catalysis | REACT_9034 (Reactome) | ||
| ADP | Arrow | REACT_1279 (Reactome) | ||
| ADP | Arrow | REACT_132 (Reactome) | ||
| ADP | Arrow | REACT_1994 (Reactome) | ||
| ADP | Arrow | REACT_2111 (Reactome) | ||
| ADP | Arrow | REACT_8998 (Reactome) | ||
| ADP | Arrow | REACT_9007 (Reactome) | ||
| ADP | Arrow | REACT_9057 (Reactome) | ||
| ADP | Arrow | REACT_9070 (Reactome) | ||
| AMP | Arrow | REACT_315 (Reactome) | ||
| ATP | REACT_1279 (Reactome) | |||
| ATP | REACT_132 (Reactome) | |||
| ATP | REACT_1673 (Reactome) | |||
| ATP | REACT_1994 (Reactome) | |||
| ATP | REACT_2111 (Reactome) | |||
| ATP | REACT_8998 (Reactome) | |||
| ATP | REACT_9007 (Reactome) | |||
| ATP | REACT_9057 (Reactome) | |||
| ATP | REACT_9070 (Reactome) | |||
| Ac-CoA | REACT_150144 (Reactome) | |||
| Ac-CoA | REACT_150456 (Reactome) | |||
| Ac-Cohesin
PDS5 WAPAL Centromere | Arrow | REACT_150144 (Reactome) | ||
| Ac-Cohesin
PDS5 WAPAL Centromere | REACT_150445 (Reactome) | |||
| Ac-Cohesin
PDS5 WAPAL Chromosomal Arm | Arrow | REACT_150456 (Reactome) | ||
| Ac-Cohesin
PDS5 WAPAL Chromosomal Arm | REACT_150264 (Reactome) | |||
| CAK | mim-catalysis | REACT_9070 (Reactome) | ||
| CDC45 | REACT_6963 (Reactome) | |||
| CDC6 | Arrow | REACT_1279 (Reactome) | ||
| CDC6 | REACT_1279 (Reactome) | |||
| CDCA5 | REACT_150264 (Reactome) | |||
| CDCA5 | REACT_150445 (Reactome) | |||
| CDK2 | REACT_8996 (Reactome) | |||
| CDK | mim-catalysis | REACT_1279 (Reactome) | ||
| CKS1B | REACT_9017 (Reactome) | |||
| CMP | Arrow | REACT_315 (Reactome) | ||
| Cdc25 A/B | mim-catalysis | REACT_9062 (Reactome) | ||
| CoA-SH | Arrow | REACT_150144 (Reactome) | ||
| CoA-SH | Arrow | REACT_150456 (Reactome) | ||
| Cohesin
PDS5 WAPAL Centromere | REACT_150144 (Reactome) | |||
| Cohesin
PDS5 WAPAL Chromosomal Arm | REACT_150456 (Reactome) | |||
| Cyclin A
Cdk2 p21/p27 complex | mim-catalysis | REACT_8995 (Reactome) | ||
| Cyclin A
Cdk2 phosphorylated substrate complex | Arrow | REACT_9007 (Reactome) | ||
| Cyclin A
Cdk2 substrate complex | REACT_9007 (Reactome) | |||
| Cyclin A
Cdk2 substrate complex | mim-catalysis | REACT_2111 (Reactome) | ||
| Cyclin A
Cdk2 substrate complex | mim-catalysis | REACT_9007 (Reactome) | ||
| Cyclin A Cdk2 complex | Arrow | REACT_9062 (Reactome) | ||
| Cyclin A Cdk2 complex | REACT_9005 (Reactome) | |||
| Cyclin A Cdk2 complex | REACT_9057 (Reactome) | |||
| Cyclin A Cdk2 complex | REACT_9070 (Reactome) | |||
| Cyclin A phospho-Cdk2 | Arrow | REACT_9057 (Reactome) | ||
| Cyclin A phospho-Cdk2 | Arrow | REACT_9070 (Reactome) | ||
| Cyclin A phospho-Cdk2 | REACT_9062 (Reactome) | |||
| Cyclin A | REACT_8996 (Reactome) | |||
| Cyclin D1 Cdk4 | REACT_132 (Reactome) | |||
| Cyclin E/A
Cdk2 multiubiquitinated phospho-p27/p21 SCF | mim-catalysis | REACT_9026 (Reactome) | ||
| Cyclin E/A
Cdk2 p27/p21 complex | REACT_8998 (Reactome) | |||
| Cyclin E/A
Cdk2 p27/p21 complex | mim-catalysis | REACT_8998 (Reactome) | ||
| Cyclin E/A
Cdk2 phospho-p27/p21 SCF | REACT_9026 (Reactome) | |||
| Cyclin E/A
Cdk2 phospho-p27/p21 | Arrow | REACT_8998 (Reactome) | ||
| Cyclin E/A
Cdk2 phospho-p27/p21 | REACT_9060 (Reactome) | |||
| Cyclin E/A Cdk2 | Arrow | REACT_9034 (Reactome) | ||
| DNA Polymerase delta tetramer | REACT_1009 (Reactome) | |||
| DNA Polymerase delta tetramer | REACT_149 (Reactome) | |||
| DNA Polymerase delta tetramer | mim-catalysis | REACT_1024 (Reactome) | ||
| DNA polymerase alpha
primase DNA polymerase alpha origin complex | REACT_1611 (Reactome) | |||
| DNA polymerase alpha primase | mim-catalysis | REACT_1611 (Reactome) | ||
| DNA polymerase alpha primase | mim-catalysis | REACT_91 (Reactome) | ||
| DNA polymerase epsilon | Arrow | REACT_1611 (Reactome) | ||
| DNA2 | Arrow | REACT_315 (Reactome) | ||
| DNA2 | REACT_1278 (Reactome) | |||
| ESCO | mim-catalysis | REACT_150144 (Reactome) | ||
| ESCO | mim-catalysis | REACT_150456 (Reactome) | ||
| FEN1 | mim-catalysis | REACT_2024 (Reactome) | ||
| GINS complex | REACT_6963 (Reactome) | |||
| GINS1 | REACT_6747 (Reactome) | |||
| GINS2 | REACT_6747 (Reactome) | |||
| GINS4 | REACT_6747 (Reactome) | |||
| GMP | Arrow | REACT_315 (Reactome) | ||
| H2O | REACT_9062 (Reactome) | |||
| LIG1 | mim-catalysis | REACT_1889 (Reactome) | ||
| MCM2 | Arrow | REACT_1303 (Reactome) | ||
| MCM3 | Arrow | REACT_1303 (Reactome) | ||
| MCM5 | Arrow | REACT_1303 (Reactome) | ||
| MCM8 | mim-catalysis | REACT_6768 (Reactome) | ||
| Mcm2-7 complex | REACT_6963 (Reactome) | |||
| Mcm2-7 complex | mim-catalysis | REACT_6922 (Reactome) | ||
| Mcm4,6,7 complex | Arrow | REACT_1303 (Reactome) | ||
| Myc/Max heterodimer | Arrow | REACT_9013 (Reactome) | ||
| NTP | REACT_1611 (Reactome) | |||
| PCNA homotrimer | REACT_1994 (Reactome) | |||
| PSF3p | REACT_6747 (Reactome) | |||
| Pi | Arrow | REACT_9062 (Reactome) | ||
| Processive complex
Okazaki fragment Flap RPA heterotrimer | REACT_1278 (Reactome) | |||
| Processive complex
Okazaki fragment Flap | REACT_2026 (Reactome) | |||
| Processive complex
Okazaki fragments Remaining Flap | Arrow | REACT_315 (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 | Arrow | REACT_1994 (Reactome) | ||
| RFC Heteropentamer
RNA primer-DNA primer origin duplex | REACT_1994 (Reactome) | |||
| RFC Heteropentamer | Arrow | REACT_351 (Reactome) | ||
| RFC Heteropentamer | REACT_1871 (Reactome) | |||
| RNA primer
origin duplex DNA polymerase alpha primase complex | Arrow | REACT_1611 (Reactome) | ||
| RNA primer
origin duplex DNA polymerase alpha primase complex | REACT_91 (Reactome) | |||
| RNA primer-DNA primer
origin duplex PCNA | Arrow | REACT_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 duplex | REACT_1871 (Reactome) | |||
| RPA heterotrimer | Arrow | REACT_315 (Reactome) | ||
| RPA heterotrimer | REACT_2026 (Reactome) | |||
| Replication Fork | REACT_6963 (Reactome) | |||
| SCF | Arrow | REACT_9034 (Reactome) | ||
| SCF | REACT_9017 (Reactome) | |||
| SCF | REACT_9060 (Reactome) | |||
| Sister Centromere | REACT_150445 (Reactome) | |||
| Sister Chromosomal Arm | REACT_150264 (Reactome) | |||
| UMP | Arrow | REACT_315 (Reactome) | ||
| Ub | REACT_1673 (Reactome) | |||
| Ub | REACT_715 (Reactome) | |||
| Ubiquitin ligase | mim-catalysis | REACT_715 (Reactome) | ||
| WEE1 | mim-catalysis | REACT_9057 (Reactome) | ||
| anaphase-promoting complex | mim-catalysis | REACT_1673 (Reactome) | ||
| dATP | REACT_91 (Reactome) | |||
| dCTP | REACT_91 (Reactome) | |||
| dGTP | REACT_91 (Reactome) | |||
| dTTP | REACT_91 (Reactome) | |||
| glycogen synthase kinase-3 beta | mim-catalysis | REACT_132 (Reactome) | ||
| p-CDC6 | REACT_1673 (Reactome) | |||
| p-S,T-ORC1 | Arrow | REACT_2111 (Reactome) | ||
| p-S,T-ORC1 | REACT_1626 (Reactome) | |||
| p-T286-CCND1 | REACT_715 (Reactome) | |||
| p21/p27 | REACT_9005 (Reactome) | |||
| p21/p27 | mim-catalysis | REACT_9005 (Reactome) | ||
| phospho | Arrow | REACT_132 (Reactome) | ||
| pre-replicative complex | Arrow | REACT_2111 (Reactome) | ||
| pre-replicative complex | REACT_2111 (Reactome) | |||
| ubiquitin | Arrow | REACT_9034 (Reactome) | ||
| ubiquitin | REACT_1626 (Reactome) | |||
| ubiquitin | REACT_9026 (Reactome) |
