Nucleotide Excision Repair (Homo sapiens)

From WikiPathways

Revision as of 12:55, 21 August 2015 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
1, 11, 15104, 8, 146, 94, 8, 141210777nucleoplasmRPA1 POLR2C ERCC1 RPA3 CDK7 GTF2H3 XAB2 TFIIHRAD23B ERCC6MNAT1 ERCC5 POLR2L RFC2 ERCC8 GTF2H1 Active Pol IIcomplex withrepaired DNAtemplate:mRNAhybridGTF2H3 POLR2J POLR2B POLR2I POLR2I ERCC3 XAB2 Transcription-coupled (TC) repair complexTranscription-coupled (TC) repair complex:Stalled Pol II complex with damaged DNA hybridRAD23BGTF2H3 damaged DNAsubstrateGTF2H2 XAB2GTF2H4 MNAT1 ERCC8 ERCC2 POLR2L XPA GTF2H1 POLR2B pre-incision complexin GG-NERPOLR2H POLR2E RAD23B POLR2F CDK7 ERCC8 Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybridPOLR2J DDB2 POLR2D XPC:HR23B:damagedDNA complexGTF2H2 MNAT1 CDK7 DDB1RPA2 Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybrid with 3' incisionGTF2H4 POLR2D DDB1 ERCC4 incision complex forGG-NERRPA3 ERCC5 GTF2H4 pre-incision complexwith open DNAbubbleCCNH RAD23B ERCC1 XPC POLR2B ERCC8ERCC5 GTF2H5 GTF2H4 ERCC6 POLR2I RPA2 POLR2K Incision complexwith 3'-inciseddamaged DNAGTF2H5 CCNH CDK7 dsDNAp-S2,S5-POLR2A ERCC5MNAT1 p-S2,S5-POLR2A GTF2H1 XPC:RAD23Bp-S2,S5-POLR2A CCNH ERCC2 DDB1 CDK7 dNTPCCNH RPA1 POLR2C RFC1 GTF2H3 MNAT1 PCNA POLR2B GTF2H2 ERCC3 RPA3 GTF2H4 GTF2H5 SSB-dsDNAERCC1 excised DNA fragmentwith lesionTCEA1DNA containingsingle strand nick(5' phosphate 3'hydroxyl) with mRNAhybridPOLR2F repaired DNAtemplate:nascentmRNA hybridPOLR2F GTF2H5 RPA2 POLR2H GTF2H1 DDB1 MNAT1 XPAGTF2H1 POLR2G CCNH ERCC2 ERCC1 RPA1 incised DNA withoutlesionERCC6 POLR2I POLR2E CDK7 RPA heterotrimerERCC4DDB2 GTF2H5 ERCC2 POLR2E ERCC5 DDB2 POLR2B ERCC4 XAB2 CCNH RFC4 POLR2L XPC DDB1 RPA3 GTF2H3 ERCC1 RPA3 ERCC2 RPA2 ERCC1:XPF complexPOLR2G damaged DNAsubstrate:nascentmRNA hybridERCC3 GTF2H4 p-S2,S5-POLR2A CCNH POLR2J POLR2K ERCC3 POLR2F XPA GTF2H5 ERCC3 POLR2C GTF2H1 CDK7 POLR2K ERCC4 POLR2C RAD23B XPA MNAT1 GTF2H4 GTF2H3 GTF2H1 DDB2Stalled Pol IIcomplex withdamaged DNA hybridXPA GTF2H4 CCNH ERCC4 GTF2H3 ERCC5 MNAT1 GTF2H5 POLR2H TCEA1 GTF2H3 POLR2D GTF2H5 ERCC1POLR2D POLR2F RAD23B XPC GTF2H5 POLR2L XPC ERCC1 RPA1 POLR2J PCNA:POLD,POLE:RPA:RFCGTF2H1 RFC3 ERCC5 RNAPolymeraseIIholoenzymecomplex(hyperphosphorylated)GTF2H2 damaged DNAsubstrate:nascentmRNA hybrid withdual incisionsGTF2H2 ERCC6 GTF2H2 ERCC1 RPA3 RPA1 ERCC3 POLR2J ERCC5 ERCC5 POLR2G POLR2D ERCC2 ERCC3 POLR2K Active Pol II transcriptioncomplex withdamaged DNA hybridXPCERCC2 POLR2H PPiTCEA1 POLR2G GTF2H2 GTF2H3 ERCC3 ERCC8 p-S2,S5-POLR2A POLR2K ERCC4 POLR2G ERCC6 MNAT1 CCNH POLR2C GTF2H4 ERCC4 DDB2 CDK7 POLR2H POLR2E ERCC3 XPC ERCC2 RFC5 XPC LIG1ERCC2 RPA2 TCEA1 POLR2I POLR2L TCEA1 RPA1 ERCC4 GTF2H2 RAD23B CDK7 GTF2H1 GTF2H2 XAB2 POLR2E RPA2 52, 3, 135555


Description

NER was first described in the model organism E. coli in the early 1960s as a process whereby bulky base damage is enzymatically removed from DNA, facilitating the recovery of DNA synthesis and cell survival. Deficient NER processes have been identified from the cells of cancer-prone patients with different variants of xeroderma pigmentosum (XP), trichothiodystrophy (TTD), and Cockayne's syndrome. These XP cells exhibited an ultraviolet radiation hypersensitivity leading to a hypermutability response to UV, offering a direct connection between deficient NER, increased mutations, and cancer. While the NER pathway in prokaryotes is unique, the pathway utilized in yeast and higher eukaryotes is highly conserved and includes a variety of proteins that interact to form complexes.
NER is involved in the repair of bulky adducts in DNA, such as UV-induced photo lesions [of both 6-4 photoproducts (6-4 pps) and cyclobutane pyrimidine dimer (CPDs)], intrastrand cross-links, large chemical adducts formed from exposure to aflatoxin, benzopyrene and other genotoxic agents. Specific proteins have been identified that participate in base damage recognition, cleavage of the damaged strand on both sides of the lesion, excision of the oligonucleotide bearing the lesion, and accessory proteins necessary for efficient function. Polymerization and ligation restore the strand to its original state. NER consists of two related pathways called global genomic repair (GG-NER) and transcription-coupled NER (TC-NER). The pathways differ in the way in which DNA damage is initially recognized, but the majority of the participating molecules are shared between these two branches of NER. GG-NER is considered to be transcription-independent, removing lesions from non-transcribed regions of genome in addition to non-transcribed strands of transcribed regions. The preferential repair of UV-induced damage in transcribed strands of active genes is known as Transcription-coupled NER (TC-NER).
Several of the proteins involved in NER are key components of the basal transcription complex TFIIH. NER proteins have also been shown to interact with the 19S regulatory subunit of the proteasome, suggesting a role in cellular regulation signal pathways. The establishment of mutant mouse models for NER genes and other DNA repair-related genes have been useful in demonstrating the associations between NER defects and cancer.

Source:Reactome.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Wang QE, Zhu Q, Wani G, Chen J, Wani AA.; ''UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2.''; PubMed Europe PMC Scholia
  2. Robu M, Shah RG, Petitclerc N, Brind'Amour J, Kandan-Kulangara F, Shah GM.; ''Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.''; PubMed Europe PMC Scholia
  3. Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH.; ''Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo.''; PubMed Europe PMC Scholia
  4. Lee KB, Wang D, Lippard SJ, Sharp PA.; ''Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro.''; PubMed Europe PMC Scholia
  5. Shiyanov P, Nag A, Raychaudhuri P.; ''Cullin 4A associates with the UV-damaged DNA-binding protein DDB.''; PubMed Europe PMC Scholia
  6. Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D.; ''Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.''; PubMed Europe PMC Scholia
  7. Winkler GS, Sugasawa K, Eker AP, de Laat WL, Hoeijmakers JH.; ''Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.''; PubMed Europe PMC Scholia
  8. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y.; ''Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.''; PubMed Europe PMC Scholia
  9. Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, Coin F, Egly JM, Tanaka K.; ''XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients.''; PubMed Europe PMC Scholia
  10. Birger Y, West KL, Postnikov YV, Lim JH, Furusawa T, Wagner JP, Laufer CS, Kraemer KH, Bustin M.; ''Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin.''; PubMed Europe PMC Scholia
  11. Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM.; ''Nucleotide excision repair driven by the dissociation of CAK from TFIIH.''; PubMed Europe PMC Scholia
  12. Brueckner F, Hennecke U, Carell T, Cramer P.; ''CPD damage recognition by transcribing RNA polymerase II.''; PubMed Europe PMC Scholia
  13. Ziani S, Nagy Z, Alekseev S, Soutoglou E, Egly JM, Coin F.; ''Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin.''; PubMed Europe PMC Scholia
  14. Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly JM.; ''Molecular structure of human TFIIH.''; PubMed Europe PMC Scholia
  15. Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL.; ''UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.''; PubMed Europe PMC Scholia
  16. Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH, Pommier Y.; ''Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.''; PubMed Europe PMC Scholia
  17. Friedberg EC.; ''How nucleotide excision repair protects against cancer.''; PubMed Europe PMC Scholia
  18. Orelli B, McClendon TB, Tsodikov OV, Ellenberger T, Niedernhofer LJ, Schärer OD.; ''The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways.''; PubMed Europe PMC Scholia
  19. Selby CP, Sancar A.; ''Cockayne syndrome group B protein enhances elongation by RNA polymerase II.''; PubMed Europe PMC Scholia
  20. Kuper J, Wolski SC, Michels G, Kisker C.; ''Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation.''; PubMed Europe PMC Scholia
  21. Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F.; ''The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA.''; PubMed Europe PMC Scholia
  22. Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S.; ''Characterization of DNA recognition by the human UV-damaged DNA-binding protein.''; PubMed Europe PMC Scholia
  23. Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH.; ''A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  24. Camenisch U, Dip R, Schumacher SB, Schuler B, Naegeli H.; ''Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.''; PubMed Europe PMC Scholia
  25. Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, Hensbergen P, Deelder A, de Groot A, Matsumoto S, Sugasawa K, Thoma N, Vermeulen W, Vrieling H, Mullenders L.; ''PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.''; PubMed Europe PMC Scholia
  26. Anindya R, Mari PO, Kristensen U, Kool H, Giglia-Mari G, Giglia-Mari G, Mullenders LH, Fousteri M, Vermeulen W, Egly JM, Svejstrup JQ.; ''A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair.''; PubMed Europe PMC Scholia
  27. Overmeer RM, Moser J, Volker M, Kool H, Tomkinson AE, van Zeeland AA, Mullenders LH, Fousteri M.; ''Replication protein A safeguards genome integrity by controlling NER incision events.''; PubMed Europe PMC Scholia
  28. Dunand-Sauthier I, Hohl M, Thorel F, Jaquier-Gubler P, Clarkson SG, Schärer OD.; ''The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity.''; PubMed Europe PMC Scholia
  29. King BS, Cooper KL, Liu KJ, Hudson LG.; ''Poly(ADP-ribose) contributes to an association between poly(ADP-ribose) polymerase-1 and xeroderma pigmentosum complementation group A in nucleotide excision repair.''; PubMed Europe PMC Scholia
  30. Park CH, Bessho T, Matsunaga T, Sancar A.; ''Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.''; PubMed Europe PMC Scholia
  31. Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K.; ''XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription.''; PubMed Europe PMC Scholia
  32. Dinant C, Ampatziadis-Michailidis G, Lans H, Tresini M, Lagarou A, Grosbart M, Theil AF, van Cappellen WA, Kimura H, Bartek J, Fousteri M, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage.''; PubMed Europe PMC Scholia
  33. Conaway RC, Conaway JW.; ''The INO80 chromatin remodeling complex in transcription, replication and repair.''; PubMed Europe PMC Scholia
  34. Mackinnon-Roy C, Stubbert LJ, McKay BC.; ''RNA interference against transcription elongation factor SII does not support its role in transcription-coupled nucleotide excision repair.''; PubMed Europe PMC Scholia
  35. Riedl T, Hanaoka F, Egly JM.; ''The comings and goings of nucleotide excision repair factors on damaged DNA.''; PubMed Europe PMC Scholia
  36. Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, Tanaka K, Shirakawa M.; ''Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA.''; PubMed Europe PMC Scholia
  37. Christmann M, Tomicic MT, Roos WP, Kaina B.; ''Mechanisms of human DNA repair: an update.''; PubMed Europe PMC Scholia
  38. Min JH, Pavletich NP.; ''Recognition of DNA damage by the Rad4 nucleotide excision repair protein.''; PubMed Europe PMC Scholia
  39. Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, Hoeijmakers JH, Demmers JA, Fousteri M, Vermeulen W, Marteijn JA.; ''UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair.''; PubMed Europe PMC Scholia
  40. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH.; ''Understanding nucleotide excision repair and its roles in cancer and ageing.''; PubMed Europe PMC Scholia
  41. Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F.; ''Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair.''; PubMed Europe PMC Scholia
  42. Sollier J, Stork CT, García-Rubio ML, Paulsen RD, Aguilera A, Cimprich KA.; ''Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability.''; PubMed Europe PMC Scholia
  43. Mourgues S, Gautier V, Lagarou A, Bordier C, Mourcet A, Slingerland J, Kaddoum L, Coin F, Vermeulen W, Gonzales de Peredo A, Monsarrat B, Mari PO, Giglia-Mari G.; ''ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair.''; PubMed Europe PMC Scholia
  44. Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J, Wani AA.; ''DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation.''; PubMed Europe PMC Scholia
  45. Balajee AS, May A, Dianova I, Bohr VA.; ''Efficient PCNA complex formation is dependent upon both transcription coupled repair and genome overall repair.''; PubMed Europe PMC Scholia
  46. Scrima A, Konícková R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thomä NH.; ''Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.''; PubMed Europe PMC Scholia
  47. Hanawalt PC, Spivak G.; ''Transcription-coupled DNA repair: two decades of progress and surprises.''; PubMed Europe PMC Scholia
  48. Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L.; ''INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway.''; PubMed Europe PMC Scholia
  49. Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T.; ''Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.''; PubMed Europe PMC Scholia
  50. Fei J, Chen J.; ''KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR).''; PubMed Europe PMC Scholia
  51. Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F.; ''Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning.''; PubMed Europe PMC Scholia
  52. Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Schärer OD, Wagner G, Ellenberger T.; ''Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA.''; PubMed Europe PMC Scholia
  53. Sarker AH, Tsutakawa SE, Kostek S, Ng C, Shin DS, Peris M, Campeau E, Tainer JA, Nogales E, Cooper PK.; ''Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome.''; PubMed Europe PMC Scholia
  54. Rossignol M, Kolb-Cheynel I, Egly JM.; ''Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH.''; PubMed Europe PMC Scholia
  55. Mathieu N, Kaczmarek N, Naegeli H.; ''Strand- and site-specific DNA lesion demarcation by the xeroderma pigmentosum group D helicase.''; PubMed Europe PMC Scholia
  56. Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K.; ''Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair.''; PubMed Europe PMC Scholia
  57. Poulsen SL, Hansen RK, Wagner SA, van Cuijk L, van Belle GJ, Streicher W, Wikström M, Choudhary C, Houtsmuller AB, Marteijn JA, Bekker-Jensen S, Mailand N.; ''RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response.''; PubMed Europe PMC Scholia
  58. Fang L, Wang X, Yamoah K, Chen PL, Pan ZQ, Huang L.; ''Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry.''; PubMed Europe PMC Scholia
  59. Jawhari A, Lainé JP, Dubaele S, Lamour V, Poterszman A, Coin F, Moras D, Egly JM.; ''p52 Mediates XPB function within the transcription/repair factor TFIIH.''; PubMed Europe PMC Scholia
  60. Epshtein V, Kamarthapu V, McGary K, Svetlov V, Ueberheide B, Proshkin S, Mironov A, Nudler E.; ''UvrD facilitates DNA repair by pulling RNA polymerase backwards.''; PubMed Europe PMC Scholia
  61. Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders LH, Fousteri MI.; ''Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner.''; PubMed Europe PMC Scholia
  62. Akita M, Tak YS, Shimura T, Matsumoto S, Okuda-Shimizu Y, Shimizu Y, Nishi R, Saitoh H, Iwai S, Mori T, Ikura T, Sakai W, Hanaoka F, Sugasawa K.; ''SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair.''; PubMed Europe PMC Scholia
  63. Oksenych V, Bernardes de Jesus B, Zhovmer A, Egly JM, Coin F.; ''Molecular insights into the recruitment of TFIIH to sites of DNA damage.''; PubMed Europe PMC Scholia
  64. Ahel D, Horejsí Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ.; ''Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.''; PubMed Europe PMC Scholia
  65. Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM.; ''Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH.''; PubMed Europe PMC Scholia
  66. Reardon JT, Ge H, Gibbs E, Sancar A, Hurwitz J, Pan ZQ.; ''Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.''; PubMed Europe PMC Scholia
  67. Groisman R, Groisman R, Kuraoka I, Chevallier O, Gaye N, Magnaldo T, Tanaka K, Kisselev AF, Harel-Bellan A, Nakatani Y.; ''CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.''; PubMed Europe PMC Scholia
  68. Vermeulen W, Fousteri M.; ''Mammalian transcription-coupled excision repair.''; PubMed Europe PMC Scholia
  69. Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, Nakazawa Y, Niimi A, Miki Y, Jaspers NG, Mullenders LH, Yamashita S, Fousteri MI, Lehmann AR.; ''Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.''; PubMed Europe PMC Scholia
  70. Donahue BA, Yin S, Taylor JS, Reines D, Hanawalt PC.; ''Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template.''; PubMed Europe PMC Scholia
  71. Groisman R, Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y.; ''The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.''; PubMed Europe PMC Scholia
  72. Moser J, Volker M, Kool H, Alekseev S, Vrieling H, Yasui A, van Zeeland AA, Mullenders LH.; ''The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions.''; PubMed Europe PMC Scholia
  73. Zotter A, Luijsterburg MS, Warmerdam DO, Ibrahim S, Nigg A, van Cappellen WA, Hoeijmakers JH, van Driel R, Vermeulen W, Houtsmuller AB.; ''Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH.''; PubMed Europe PMC Scholia
  74. Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F.; ''Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  75. Perez-Oliva AB, Lachaud C, Szyniarowski P, Muñoz I, Macartney T, Hickson I, Rouse J, Alessi DR.; ''USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage responses.''; PubMed Europe PMC Scholia
  76. Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMed Europe PMC Scholia
  77. Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura K, Ogi T.; ''Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair.''; PubMed Europe PMC Scholia
  78. Wittschieben BØ, Iwai S, Wood RD.; ''DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.''; PubMed Europe PMC Scholia
  79. Wakasugi M, Kasashima H, Fukase Y, Imura M, Imai R, Yamada S, Cleaver JE, Matsunaga T.; ''Physical and functional interaction between DDB and XPA in nucleotide excision repair.''; PubMed Europe PMC Scholia
  80. He Z, Henricksen LA, Wold MS, Ingles CJ.; ''RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.''; PubMed Europe PMC Scholia
  81. Volker M, Moné MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH.; ''Sequential assembly of the nucleotide excision repair factors in vivo.''; PubMed Europe PMC Scholia
  82. Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapić-Otrin V, Levine AS.; ''The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.''; PubMed Europe PMC Scholia
  83. Hofmann RM, Pickart CM.; ''Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.''; PubMed Europe PMC Scholia
  84. Sarkar S, Kiely R, McHugh PJ.; ''The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair.''; PubMed Europe PMC Scholia
  85. Mocquet V, Lainé JP, Riedl T, Yajin Z, Lee MY, Egly JM.; ''Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step.''; PubMed Europe PMC Scholia
  86. Mathieu N, Kaczmarek N, Rüthemann P, Luch A, Naegeli H.; ''DNA quality control by a lesion sensor pocket of the xeroderma pigmentosum group D helicase subunit of TFIIH.''; PubMed Europe PMC Scholia
  87. Giglia-Mari G, Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W.; ''A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A.''; PubMed Europe PMC Scholia
  88. Fischer ES, Scrima A, Böhm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thomä NH.; ''The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation.''; PubMed Europe PMC Scholia
  89. Staresincic L, Fagbemi AF, Enzlin JH, Gourdin AM, Wijgers N, Dunand-Sauthier I, Giglia-Mari G, Giglia-Mari G, Clarkson SG, Vermeulen W, Schärer OD.; ''Coordination of dual incision and repair synthesis in human nucleotide excision repair.''; PubMed Europe PMC Scholia
  90. Camenisch U, Träutlein D, Clement FC, Fei J, Leitenstorfer A, Ferrando-May E, Naegeli H.; ''Two-stage dynamic DNA quality check by xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  91. de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, Hoeijmakers JH.; ''DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.''; PubMed Europe PMC Scholia
  92. Takedachi A, Saijo M, Tanaka K.; ''DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA.''; PubMed Europe PMC Scholia
  93. Fitch ME, Nakajima S, Yasui A, Ford JM.; ''In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.''; PubMed Europe PMC Scholia
  94. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, Hanaoka F.; ''UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.''; PubMed Europe PMC Scholia
  95. Coin F, Oksenych V, Egly JM.; ''Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair.''; PubMed Europe PMC Scholia
  96. Oh KS, Imoto K, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH.; ''Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells.''; PubMed Europe PMC Scholia
  97. Kuraoka I, Ito S, Wada T, Hayashida M, Lee L, Saijo M, Nakatsu Y, Matsumoto M, Matsunaga T, Handa H, Qin J, Nakatani Y, Tanaka K.; ''Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair.''; PubMed Europe PMC Scholia
  98. van Cuijk L, van Belle GJ, van Belle GJ, Turkyilmaz Y, Poulsen SL, Janssens RC, Theil AF, Sabatella M, Lans H, Mailand N, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair.''; PubMed Europe PMC Scholia
  99. Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMed Europe PMC Scholia
  100. Morris DP, Michelotti GA, Schwinn DA.; ''Evidence that phosphorylation of the RNA polymerase II carboxyl-terminal repeats is similar in yeast and humans.''; PubMed Europe PMC Scholia
  101. Lindahl T, Wood RD.; ''Quality control by DNA repair.''; PubMed Europe PMC Scholia
  102. Araújo SJ, Wood RD.; ''Protein complexes in nucleotide excision repair.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115027view16:56, 25 January 2021ReactomeTeamReactome version 75
113472view11:54, 2 November 2020ReactomeTeamReactome version 74
112671view16:06, 9 October 2020ReactomeTeamReactome version 73
101588view11:45, 1 November 2018ReactomeTeamreactome version 66
101124view21:29, 31 October 2018ReactomeTeamreactome version 65
100652view20:03, 31 October 2018ReactomeTeamreactome version 64
100202view16:48, 31 October 2018ReactomeTeamreactome version 63
99753view15:14, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93777view13:35, 16 August 2017ReactomeTeamreactome version 61
93305view11:19, 9 August 2017ReactomeTeamreactome version 61
88077view09:04, 26 July 2016RyanmillerOntology Term : 'DNA repair pathway' added !
88076view09:02, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86389view09:16, 11 July 2016ReactomeTeamreactome version 56
83072view09:53, 18 November 2015ReactomeTeamVersion54
81391view12:55, 21 August 2015ReactomeTeamVersion53
76859view08:13, 17 July 2014ReactomeTeamFixed remaining interactions
76564view11:54, 16 July 2014ReactomeTeamFixed remaining interactions
75897view09:55, 11 June 2014ReactomeTeamRe-fixing comment source
75597view10:44, 10 June 2014ReactomeTeamReactome 48 Update
74952view13:47, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74596view08:38, 30 April 2014ReactomeTeamReactome46
42219view00:30, 8 March 2011MaintBotModified categories
42218view00:23, 8 March 2011MaintBot
42217view00:22, 8 March 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Active Pol II

complex with repaired DNA template:mRNA

hybrid		ComplexR-HSA-110296 (Reactome)
Active Pol II

transcription complex with

damaged DNA hybrid		ComplexR-HSA-110292 (Reactome)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
DDB1 ProteinQ16531 (Uniprot-TrEMBL)
DDB1ProteinQ16531 (Uniprot-TrEMBL)
DDB2 ProteinQ92466 (Uniprot-TrEMBL)
DDB2ProteinQ92466 (Uniprot-TrEMBL)
DNA containing

single strand nick (5' phosphate 3' hydroxyl) with mRNA

hybrid		R-NUL-5688511 (Reactome)
ERCC1 ProteinP07992 (Uniprot-TrEMBL)
ERCC1:XPF complexComplexR-HSA-109943 (Reactome)
ERCC1ProteinP07992 (Uniprot-TrEMBL)
ERCC2 ProteinP18074 (Uniprot-TrEMBL)
ERCC3 ProteinP19447 (Uniprot-TrEMBL)
ERCC4 ProteinQ92889 (Uniprot-TrEMBL)
ERCC4ProteinQ92889 (Uniprot-TrEMBL)
ERCC5 ProteinP28715 (Uniprot-TrEMBL)
ERCC5ProteinP28715 (Uniprot-TrEMBL)
ERCC6 ProteinQ03468 (Uniprot-TrEMBL)
ERCC6ProteinQ03468 (Uniprot-TrEMBL)
ERCC8 ProteinQ13216 (Uniprot-TrEMBL)
ERCC8ProteinQ13216 (Uniprot-TrEMBL)
GTF2H1 ProteinP32780 (Uniprot-TrEMBL)
GTF2H2 ProteinQ13888 (Uniprot-TrEMBL)
GTF2H3 ProteinQ13889 (Uniprot-TrEMBL)
GTF2H4 ProteinQ92759 (Uniprot-TrEMBL)
GTF2H5 ProteinQ6ZYL4 (Uniprot-TrEMBL)
Incision complex

with 3'-incised

damaged DNA		ComplexR-HSA-109947 (Reactome)
LIG1ProteinP18858 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
PCNA ProteinP12004 (Uniprot-TrEMBL)
PCNA:POLD,POLE:RPA:RFCComplexR-HSA-5651799 (Reactome)
POLR2B ProteinP30876 (Uniprot-TrEMBL)
POLR2C ProteinP19387 (Uniprot-TrEMBL)
POLR2D ProteinO15514 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2F ProteinP61218 (Uniprot-TrEMBL)
POLR2G ProteinP62487 (Uniprot-TrEMBL)
POLR2H ProteinP52434 (Uniprot-TrEMBL)
POLR2I ProteinP36954 (Uniprot-TrEMBL)
POLR2J ProteinP52435 (Uniprot-TrEMBL)
POLR2K ProteinP53803 (Uniprot-TrEMBL)
POLR2L ProteinP62875 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
RAD23B ProteinP54727 (Uniprot-TrEMBL)
RAD23BProteinP54727 (Uniprot-TrEMBL)
RFC1 ProteinP35251 (Uniprot-TrEMBL)
RFC2 ProteinP35250 (Uniprot-TrEMBL)
RFC3 ProteinP40938 (Uniprot-TrEMBL)
RFC4 ProteinP35249 (Uniprot-TrEMBL)
RFC5 ProteinP40937 (Uniprot-TrEMBL)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)		ComplexR-HSA-109909 (Reactome)
RPA heterotrimerComplexR-HSA-68462 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
SSB-dsDNAR-HSA-110340 (Reactome)
Stalled Pol II

complex with

damaged DNA hybrid		ComplexR-HSA-110293 (Reactome)
TCEA1 ProteinP23193 (Uniprot-TrEMBL)
TCEA1ProteinP23193 (Uniprot-TrEMBL)
TFIIHComplexR-HSA-109634 (Reactome)
Transcription-coupled (TC) repair complex:Stalled Pol II complex with damaged DNA hybridComplexR-HSA-5688512 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybrid with 3' incisionComplexR-HSA-5688517 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybridComplexR-HSA-5688515 (Reactome)
Transcription-coupled (TC) repair complexComplexR-HSA-110276 (Reactome)
XAB2 ProteinQ9HCS7 (Uniprot-TrEMBL)
XAB2ProteinQ9HCS7 (Uniprot-TrEMBL)
XPA ProteinP23025 (Uniprot-TrEMBL)
XPAProteinP23025 (Uniprot-TrEMBL)
XPC ProteinQ01831 (Uniprot-TrEMBL)
XPC:HR23B:damaged DNA complexComplexR-HSA-109940 (Reactome)
XPC:RAD23BComplexR-HSA-109938 (Reactome)
XPCProteinQ01831 (Uniprot-TrEMBL)
dNTPMetaboliteCHEBI:16516 (ChEBI)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions		R-NUL-110303 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid		R-NUL-110291 (Reactome)
damaged DNA substrateR-NUL-109939 (Reactome)
dsDNAR-HSA-5649637 (Reactome)
excised DNA fragment with lesionR-NUL-109960 (Reactome)
incised DNA without lesionR-NUL-109961 (Reactome)
incision complex for GG-NERComplexR-HSA-109946 (Reactome)
p-S2,S5-POLR2A ProteinP24928 (Uniprot-TrEMBL)
pre-incision complex in GG-NERComplexR-HSA-109941 (Reactome)
pre-incision complex

with open DNA

bubble		ComplexR-HSA-109945 (Reactome)
repaired DNA

template:nascent

mRNA hybrid		R-NUL-110295 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
Active Pol II

complex with repaired DNA template:mRNA

hybrid		ArrowR-HSA-109980 (Reactome)
Active Pol II

transcription complex with

damaged DNA hybrid		ArrowR-HSA-110301 (Reactome)
Active Pol II

transcription complex with

damaged DNA hybrid		R-HSA-109972 (Reactome)
DDB1ArrowR-HSA-73939 (Reactome)
DDB1R-HSA-73936 (Reactome)
DDB2ArrowR-HSA-73939 (Reactome)
DDB2R-HSA-73936 (Reactome)
DNA containing

single strand nick (5' phosphate 3' hydroxyl) with mRNA

hybrid		ArrowR-HSA-110305 (Reactome)
DNA containing

single strand nick (5' phosphate 3' hydroxyl) with mRNA

hybrid		R-HSA-109978 (Reactome)
ERCC1:XPF complexArrowR-HSA-109955 (Reactome)
ERCC1:XPF complexArrowR-HSA-73939 (Reactome)
ERCC1:XPF complexR-HSA-109953 (Reactome)
ERCC1:XPF complexR-HSA-109973 (Reactome)
ERCC1R-HSA-109955 (Reactome)
ERCC4R-HSA-109955 (Reactome)
ERCC5ArrowR-HSA-73939 (Reactome)
ERCC5R-HSA-109973 (Reactome)
ERCC5R-HSA-73936 (Reactome)
ERCC6R-HSA-109973 (Reactome)
ERCC8R-HSA-109973 (Reactome)
Incision complex

with 3'-incised

damaged DNA		ArrowR-HSA-73938 (Reactome)
Incision complex

with 3'-incised

damaged DNA		R-HSA-73939 (Reactome)
Incision complex

with 3'-incised

damaged DNA		mim-catalysisR-HSA-73939 (Reactome)
LIG1mim-catalysisR-HSA-109978 (Reactome)
LIG1mim-catalysisR-HSA-74968 (Reactome)
PCNA:POLD,POLE:RPA:RFCmim-catalysisR-HSA-109968 (Reactome)
PCNA:POLD,POLE:RPA:RFCmim-catalysisR-HSA-110305 (Reactome)
PPiArrowR-HSA-109968 (Reactome)
PPiArrowR-HSA-110305 (Reactome)
R-HSA-109948 (Reactome) XPC is mutated in individuals with xeroderma pigmentosum from genetic Complementation Group C (XP-C). It forms a tight heterodimeric complex with human Rad 23B homolog, HR23B and is thought to bind to the damaged site with lesion first, triggering subsequent reactions.
R-HSA-109949 (Reactome) Disruption of normal Watson-Crick base pairing and altered chemistry in the damaged strand involving bases may act as signals of damage that are recognized by XPC:HR23B complex.
R-HSA-109953 (Reactome) ERCC1-XPF complex with 5' endonuclease activity binds to the pre-incision complex around the bubble structure to form an active incision complex.
R-HSA-109955 (Reactome) ERCC1 binds ERCC4 (XPF) to form a heterodimeric ERCC1:ERCC4 (ERCC1:XPF) complex with a DNA endonuclease activity, where ERCC4 is the catalytic subunit. Suitable substrates for the ERCC1:ERCC4 endonuclease are single strand DNA (ssDNA) and ssDNA region of a duplex DNA with an open bubble structure (Park et al. 1995).
R-HSA-109968 (Reactome) The DNA replication complex consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis after the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5). Depending on additional DNA damage present and the consequent PCNA monoubiquitination, DNA polymerase kappa (POLK) may also be involved in gap-filling DNA synthesis during nucleotide excision repair (NER) (Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
R-HSA-109972 (Reactome) At the site of damage, the Pol II complex is arrested resulting in reduced levels of transcription. Several models have been proposed to explain the mechanism of this transcriptional downregulation. These include a. hyperphosphorylation of Pol II resulting in aborted entry to new pre-initiation complexes b. sequestration of TATA-binding proteins (TBP) c. enhanced use of TFIIH complexes for repair purposes precluding their use in transcription.

R-HSA-109973 (Reactome) A proper assembly of repair complex may require displacement of Pol II from the damage site exposing a significant length of the corresponding template DNA with the lesions. Speculations on the mode of this displacement of Pol II are available from experimental evidences: a. CSB mediated dissociation of Pol II b. degradation of Pol II c. CSB mediated remodeling of damaged DNA-RNA PII interface etc.
The TC-repair complex now consists of damaged DNA template: nascent mRNA hybrid. The damage site needs to be exposed to subsequent endonuclease activities.

R-HSA-109974 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'Stalled Pol II complex with damaged DNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present.

This reaction takes place in the 'nucleus'.

R-HSA-109975 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.

R-HSA-109976 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'excised DNA fragment with lesion', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.

R-HSA-109978 (Reactome) At the beginning of this reaction, 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA ligase I ', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'repaired DNA template:nascent mRNA hybrid', and 1 molecule of 'DNA ligase I ' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA ligase activity' of 'DNA ligase I '.

R-HSA-109980 (Reactome) At the beginning of this reaction, 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'repaired DNA template:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Active Pol II complex with repaired DNA template:mRNA hybrid' is present.

This reaction takes place in the 'nucleus'.

R-HSA-110301 (Reactome) An active Pol II complex consisting mainly of the Pol II holoenzyme transcribes the damaged DNA template.

R-HSA-110305 (Reactome) After the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5) the resulting gap is filled by DNA synthesis. The DNA replication complex consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs the gap filling. Depending on additional DNA damage present and the consequent PCNA monoubiquitination, DNA polymerase kappa (POLK) may also be involved (Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
R-HSA-73934 (Reactome) Two DNA helicases XPG and XPD, which are part of TFIIH, unwind DNA duplex around this lesion to form an open bubble structure that exposes the damaged site.
R-HSA-73936 (Reactome) Transcription factor II H (TFIIH) and XPG are added to the damaged site on the DNA to form a pre-incision complex along with lesioned DNA template.
R-HSA-73938 (Reactome) The cleavage of the damaged strand of DNA 3' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The incision is carried out by XPG.
R-HSA-73939 (Reactome) The cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The incision is carried out by ERCC1-XPF complex.
R-HSA-74968 (Reactome) DNA Ligase 1 ligates the newly synthesized fragment to the gap in the template DNA.
RAD23BR-HSA-109948 (Reactome)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)		ArrowR-HSA-109974 (Reactome)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)		R-HSA-109980 (Reactome)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)		R-HSA-110301 (Reactome)
RPA heterotrimerArrowR-HSA-73939 (Reactome)
RPA heterotrimerR-HSA-73936 (Reactome)
SSB-dsDNAArrowR-HSA-109968 (Reactome)
SSB-dsDNAR-HSA-74968 (Reactome)
Stalled Pol II

complex with

damaged DNA hybrid		ArrowR-HSA-109972 (Reactome)
Stalled Pol II

complex with

damaged DNA hybrid		R-HSA-109973 (Reactome)
TCEA1R-HSA-109973 (Reactome)
TFIIHArrowR-HSA-73939 (Reactome)
TFIIHR-HSA-109973 (Reactome)
TFIIHR-HSA-73936 (Reactome)
Transcription-coupled (TC) repair complex:Stalled Pol II complex with damaged DNA hybridArrowR-HSA-109973 (Reactome)
Transcription-coupled (TC) repair complex:Stalled Pol II complex with damaged DNA hybridR-HSA-109974 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybrid with 3' incisionArrowR-HSA-109975 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybrid with 3' incisionR-HSA-109976 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybrid with 3' incisionmim-catalysisR-HSA-109976 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybridArrowR-HSA-109974 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybridR-HSA-109975 (Reactome)
Transcription-coupled (TC) repair complex:damaged DNA substrate:nascent mRNA hybridmim-catalysisR-HSA-109975 (Reactome)
Transcription-coupled (TC) repair complexArrowR-HSA-109976 (Reactome)
XAB2R-HSA-109973 (Reactome)
XPAArrowR-HSA-73939 (Reactome)
XPAR-HSA-73936 (Reactome)
XPC:HR23B:damaged DNA complexArrowR-HSA-109949 (Reactome)
XPC:HR23B:damaged DNA complexR-HSA-73936 (Reactome)
XPC:RAD23BArrowR-HSA-109948 (Reactome)
XPC:RAD23BArrowR-HSA-73939 (Reactome)
XPC:RAD23BR-HSA-109949 (Reactome)
XPCR-HSA-109948 (Reactome)
dNTPR-HSA-109968 (Reactome)
dNTPR-HSA-110305 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions		ArrowR-HSA-109976 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions		R-HSA-110305 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid		R-HSA-110301 (Reactome)
damaged DNA substrateR-HSA-109949 (Reactome)
dsDNAArrowR-HSA-74968 (Reactome)
excised DNA fragment with lesionArrowR-HSA-109976 (Reactome)
excised DNA fragment with lesionArrowR-HSA-73939 (Reactome)
incised DNA without lesionArrowR-HSA-73939 (Reactome)
incised DNA without lesionR-HSA-109968 (Reactome)
incision complex for GG-NERArrowR-HSA-109953 (Reactome)
incision complex for GG-NERR-HSA-73938 (Reactome)
incision complex for GG-NERmim-catalysisR-HSA-73938 (Reactome)
pre-incision complex in GG-NERArrowR-HSA-73936 (Reactome)
pre-incision complex in GG-NERR-HSA-73934 (Reactome)
pre-incision complex in GG-NERmim-catalysisR-HSA-73934 (Reactome)
pre-incision complex

with open DNA

bubble		ArrowR-HSA-73934 (Reactome)
pre-incision complex

with open DNA

bubble		R-HSA-109953 (Reactome)
repaired DNA

template:nascent

mRNA hybrid		ArrowR-HSA-109978 (Reactome)
repaired DNA

template:nascent

mRNA hybrid		R-HSA-109980 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1980"
Personal tools