Nucleotide Excision Repair (Homo sapiens)

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2, 5, 81, 694499XPCHR23B complex pre-incision complex in GG-NER RNA Polymerase II holoenzyme complex TFIIH XPCHR23Bdamaged DNA complex RPA heterotrimer TFIIH RNA Polymerase II holoenzyme complex RNA Polymerase II holoenzyme complex RPA heterotrimer CAK DNA polymerase epsilon DNA Polymerase delta tetramer Stalled Pol II in TC-NER CAK ERCC1XPF complex RNA Polymerase II holoenzyme complex RPA heterotrimer RPA heterotrimer XPCHR23Bdamaged DNA complex Active Pol II complex with repaired DNA templatemRNA hybrid XPCHR23B complex ERCC1XPF complex PCNA homotrimer XPCHR23B complex XPCHR23B complex RPA heterotrimer pre-incision complex with open DNA bubble TFIIH ERCC1XPF complex CAK incision complex for GG-NER RFC Heteropentamer pre-incision complex with open DNA bubble TFIIH DNA Polymerase delta tetramer CAK XPCHR23B complex Transcription-coupled CAK CAK RNA Polymerase II holoenzyme complex Stalled Pol II complex with damaged DNA hybrid XPCHR23B complex TFIIH Incision complex with 3'-incised damaged DNA Active Pol II transcription complex with damaged DNA hybrid ERCC1XPF complex TFIIH nucleoplasmERCC5 DDB1 RAD23B DDB1POLR2C GTF2H3 CDK7 POLD3 POLR2K RAD23B DDB2 ERCC4CCNH POLR2E POLR2B POLR2B DNA polymerase epsilonGTF2H1POLR2E GTF2H4 XPAPOLR2K LIG1POLR2G POLR2L CDK7 POLD2 CCNH POLR2J dNTPPOLR2E Stalled Pol II complex with damaged DNA hybridDDB2MNAT1 RPA1 GTF2H2 RFC4 ERCC1XPF complexIncision complex with 3'-incised damaged DNAGTF2H1POLR2H POLR2FXPARPA1 RFC HeteropentamerRAD23B MNAT1 damaged DNA substratenascent mRNA hybridnewly synthesized DNA fragmentPOLD4 GTF2H4 ERCC5 CCNH newly synthesized DNA fragmentRPA2 newly synthesized DNA fragmentRepaired double-stranded DNAPOLR2H CDK7 pre-incision complex in GG-NERERCC2 ERCC3 dNTPPOLD4 POLR2I POLR2C GTF2H4 DNA Polymerase delta tetramerPOLE2 GTF2H3 ERCC4 DDB1 damaged DNA substratenascent mRNA hybrid with 3' incisionRNA Polymerase II holoenzyme complex repaired DNA templatenascent mRNA hybridPCNA homotrimerRAD23BDNA Polymerase delta tetramerTCEA1POLR2J Active Pol II complex with repaired DNA templatemRNA hybridRPA3 POLR2B POLR2L TFIIHERCC2 XPCHR23Bdamaged DNA complexRAD23B newly synthesized DNA fragmentPOLR2C POLR2DPOLR2C incision complex for GG-NERERCC8RPA2 GTF2H4 RPA3 POLD1 RPA2 POLR2I POLR2G RPA2 ERCC4 newly synthesized DNA fragmentGTF2H1XPARAD23B p-S2,S5-POLR2A XAB2 CCNH ERCC2 POLD2 incised DNA without lesionp-S2,S5-POLR2A RPA3 POLR2H CDK7 POLR2DERCC5 POLR2C POLR2FMNAT1 POLR2E MNAT1 XPC GTF2H1POLR2K incised DNA without lesionERCC3 DDB2 DDB2 XPARPA3 XPC GTF2H2 CCNH RPA1 POLR2I GTF2H4 POLR2DGTF2H3 POLR2J ERCC3 POLE ERCC2 ERCC2 p-S2,S5-POLR2A RPA heterotrimerCDK7 RFC1 ERCC3 ERCC6 GTF2H3 ERCC1 MNAT1 POLR2G GTF2H3 GTF2H1PCNA pre-incision complex with open DNA bubbleXPC CCNH XPC ERCC5 ERCC4 POLR2J POLR2FPOLR2L POLR2B CDK7 Transcription-coupled POLR2B POLR2L GTF2H2 RPA3 RPA2 ERCC1 Active Pol II transcription complex with damaged DNA hybridPOLR2Dnewly synthesized DNA fragmentERCC1ERCC5DDB1 POLR2FERCC6p-S2,S5-POLR2A POLR2DdNTPGTF2H2 ERCC1 POLR2I DDB2 ERCC3 POLD1 ERCC1 TCEA1 POLR2Fp-S2,S5-POLR2A incised DNA without lesionGTF2H1ERCC2 Stalled Pol II in TC-NERPOLR2L POLR2K POLR2K XAB2damaged DNA substratePOLR2H POLR2I GTF2H3 RPA1 RFC5 MNAT1 POLR2G XPCHR23B complexRFC3 POLR2G POLD3 DDB1 excised DNA fragment with lesionERCC8 ERCC3 XPC incised DNA without lesionPOLR2H XPC damaged DNA substratenascent mRNA hybrid with dual incisionsRAD23B RFC2 ERCC5 GTF2H4 POLR2J GTF2H2 RPA1 XPCPOLR2E GTF2H2 dNTPERCC4 XPA373333


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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.


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  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 transcription complex with damaged DNA hybridComplexREACT_3609 (Reactome)
Active Pol II complex with repaired DNA template mRNA hybridComplexREACT_2462 (Reactome)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
DDB1 ProteinQ16531 (Uniprot-TrEMBL)
DDB1ProteinQ16531 (Uniprot-TrEMBL)
DDB2 ProteinQ92466 (Uniprot-TrEMBL)
DDB2ProteinQ92466 (Uniprot-TrEMBL)
DNA Polymerase delta tetramerComplexREACT_5801 (Reactome)
DNA polymerase epsilonComplexREACT_4621 (Reactome)
ERCC1 XPF complexComplexREACT_3454 (Reactome)
ERCC1 ProteinP07992 (Uniprot-TrEMBL)
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)
GTF2H1ProteinP32780 (Uniprot-TrEMBL)
GTF2H2 ProteinQ13888 (Uniprot-TrEMBL)
GTF2H3 ProteinQ13889 (Uniprot-TrEMBL)
GTF2H4 ProteinQ92759 (Uniprot-TrEMBL)
Incision complex with 3'-incised damaged DNAComplexREACT_5099 (Reactome)
LIG1ProteinP18858 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
PCNA ProteinP12004 (Uniprot-TrEMBL)
PCNA homotrimerComplexREACT_2542 (Reactome)
POLD1 ProteinP28340 (Uniprot-TrEMBL)
POLD2 ProteinP49005 (Uniprot-TrEMBL)
POLD3 ProteinQ15054 (Uniprot-TrEMBL)
POLD4 ProteinQ9HCU8 (Uniprot-TrEMBL)
POLE ProteinQ07864 (Uniprot-TrEMBL)
POLE2 ProteinP56282 (Uniprot-TrEMBL)
POLR2B ProteinP30876 (Uniprot-TrEMBL)
POLR2C ProteinP19387 (Uniprot-TrEMBL)
POLR2DProteinO15514 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2FProteinP61218 (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)
RAD23B ProteinP54727 (Uniprot-TrEMBL)
RAD23BProteinP54727 (Uniprot-TrEMBL)
RFC HeteropentamerComplexREACT_4881 (Reactome)
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 ComplexREACT_4889 (Reactome)
RPA heterotrimerComplexREACT_3427 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
Repaired double-stranded DNAREACT_4318 (Reactome)
Stalled Pol II complex with damaged DNA hybridComplexREACT_3072 (Reactome)
Stalled Pol II in TC-NERComplexREACT_4443 (Reactome)
TCEA1 ProteinP23193 (Uniprot-TrEMBL)
TCEA1ProteinP23193 (Uniprot-TrEMBL)
TFIIHComplexREACT_3832 (Reactome)
Transcription-coupled ComplexREACT_3969 (Reactome)
XAB2 ProteinQ9HCS7 (Uniprot-TrEMBL)
XAB2ProteinQ9HCS7 (Uniprot-TrEMBL)
XPAProteinP23025 (Uniprot-TrEMBL)
XPC

HR23B

damaged DNA complex		ComplexREACT_3245 (Reactome)
XPC HR23B complexComplexREACT_4017 (Reactome)
XPC ProteinQ01831 (Uniprot-TrEMBL)
XPCProteinQ01831 (Uniprot-TrEMBL)
dNTPREACT_2960 (Reactome)
damaged DNA substrate nascent mRNA hybrid with 3' incisionREACT_2845 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsREACT_5428 (Reactome)
damaged DNA substrate nascent mRNA hybridREACT_3022 (Reactome)
damaged DNA substrateREACT_2765 (Reactome)
excised DNA fragment with lesionREACT_2556 (Reactome)
incised DNA without lesionREACT_3852 (Reactome)
incision complex for GG-NERComplexREACT_5159 (Reactome)
newly synthesized DNA fragmentREACT_3448 (Reactome)
p-S2,S5-POLR2A ProteinP24928 (Uniprot-TrEMBL)
pre-incision complex in GG-NERComplexREACT_5795 (Reactome)
pre-incision complex with open DNA bubbleComplexREACT_5689 (Reactome)
repaired DNA template nascent mRNA hybridREACT_5433 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
DDB1ArrowREACT_1311 (Reactome)
DDB1REACT_1492 (Reactome)
DDB2ArrowREACT_1311 (Reactome)
DDB2REACT_1492 (Reactome)
DNA Polymerase delta tetramerArrowREACT_1196 (Reactome)
DNA Polymerase delta tetramerArrowREACT_465 (Reactome)
DNA Polymerase delta tetramerREACT_1196 (Reactome)
DNA Polymerase delta tetramerREACT_465 (Reactome)
DNA Polymerase delta tetramermim-catalysisREACT_1196 (Reactome)
DNA Polymerase delta tetramermim-catalysisREACT_465 (Reactome)
DNA polymerase epsilonArrowREACT_353 (Reactome)
DNA polymerase epsilonArrowREACT_677 (Reactome)
DNA polymerase epsilonREACT_353 (Reactome)
DNA polymerase epsilonREACT_677 (Reactome)
DNA polymerase epsilonmim-catalysisREACT_353 (Reactome)
DNA polymerase epsilonmim-catalysisREACT_677 (Reactome)
ERCC1 XPF complexArrowREACT_1311 (Reactome)
ERCC1 XPF complexREACT_1584 (Reactome)
ERCC1 XPF complexREACT_2163 (Reactome)
ERCC1REACT_1438 (Reactome)
ERCC4REACT_1438 (Reactome)
ERCC5ArrowREACT_1311 (Reactome)
ERCC5REACT_1492 (Reactome)
ERCC5REACT_1584 (Reactome)
ERCC6REACT_1584 (Reactome)
ERCC8REACT_1584 (Reactome)
Incision complex with 3'-incised damaged DNAmim-catalysisREACT_1311 (Reactome)
LIG1ArrowREACT_2181 (Reactome)
LIG1ArrowREACT_527 (Reactome)
LIG1REACT_2181 (Reactome)
LIG1REACT_527 (Reactome)
LIG1mim-catalysisREACT_2181 (Reactome)
LIG1mim-catalysisREACT_527 (Reactome)
PCNA homotrimerArrowREACT_1196 (Reactome)
PCNA homotrimerArrowREACT_353 (Reactome)
PCNA homotrimerArrowREACT_465 (Reactome)
PCNA homotrimerArrowREACT_677 (Reactome)
PCNA homotrimerREACT_1196 (Reactome)
PCNA homotrimerREACT_353 (Reactome)
PCNA homotrimerREACT_465 (Reactome)
PCNA homotrimerREACT_677 (Reactome)
RAD23BREACT_1984 (Reactome)
REACT_1033 (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.

REACT_1124 (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.

REACT_1196 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA Polymerase delta tetramer', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA Polymerase delta tetramer', 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 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.

REACT_1274 (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'.

REACT_1284 (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'.

REACT_1311 (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.

REACT_1438 (Reactome) At the beginning of this reaction, 1 molecule of 'ERCC1, DNA excision repair protein', and 1 molecule of 'XPF protein' are present. At the end of this reaction, 1 molecule of 'ERCC1:XPF complex' is present.

This reaction takes place in the 'nucleus'.

REACT_1453 (Reactome) An active Pol II complex consisting mainly of the Pol II holoenzyme transcribes the damaged DNA template.

REACT_1492 (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.

REACT_1584 (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.

REACT_1947 (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.

REACT_1984 (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

REACT_1987 (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.

REACT_2163 (Reactome) ERCC1-XPF complex with 5’ endonuclease activity binds to this pre-incision complex around the bubble structure to form an active incision complex.

REACT_2181 (Reactome) DNA Ligase 1 ligates the newly synthesized fragment to the gap in the template DNA.

REACT_353 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA polymerase epsilon' are present.

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

REACT_465 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA Polymerase delta tetramer' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA Polymerase delta tetramer' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.

REACT_527 (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 '.

REACT_551 (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'.

REACT_677 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA polymerase epsilon', 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 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'.

REACT_811 (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'.

RFC HeteropentamerArrowREACT_1196 (Reactome)
RFC HeteropentamerArrowREACT_353 (Reactome)
RFC HeteropentamerArrowREACT_465 (Reactome)
RFC HeteropentamerArrowREACT_677 (Reactome)
RFC HeteropentamerREACT_1196 (Reactome)
RFC HeteropentamerREACT_353 (Reactome)
RFC HeteropentamerREACT_465 (Reactome)
RFC HeteropentamerREACT_677 (Reactome)
RNA Polymerase II holoenzyme complex REACT_1453 (Reactome)
RPA heterotrimerArrowREACT_1196 (Reactome)
RPA heterotrimerArrowREACT_1311 (Reactome)
RPA heterotrimerArrowREACT_353 (Reactome)
RPA heterotrimerArrowREACT_465 (Reactome)
RPA heterotrimerArrowREACT_677 (Reactome)
RPA heterotrimerREACT_1196 (Reactome)
RPA heterotrimerREACT_1492 (Reactome)
RPA heterotrimerREACT_353 (Reactome)
RPA heterotrimerREACT_465 (Reactome)
RPA heterotrimerREACT_677 (Reactome)
Repaired double-stranded DNAArrowREACT_2181 (Reactome)
Stalled Pol II complex with damaged DNA hybridArrowREACT_1584 (Reactome)
Stalled Pol II complex with damaged DNA hybridREACT_1284 (Reactome)
Stalled Pol II complex with damaged DNA hybridREACT_1584 (Reactome)
Stalled Pol II in TC-NERArrowREACT_1284 (Reactome)
Stalled Pol II in TC-NERREACT_551 (Reactome)
TCEA1REACT_1584 (Reactome)
TFIIHArrowREACT_1311 (Reactome)
TFIIHREACT_1492 (Reactome)
TFIIHREACT_1584 (Reactome)
Transcription-coupled ArrowREACT_1274 (Reactome)
Transcription-coupled ArrowREACT_1284 (Reactome)
Transcription-coupled ArrowREACT_1584 (Reactome)
Transcription-coupled ArrowREACT_811 (Reactome)
Transcription-coupled REACT_1274 (Reactome)
Transcription-coupled REACT_1284 (Reactome)
Transcription-coupled REACT_811 (Reactome)
Transcription-coupled mim-catalysisREACT_1274 (Reactome)
Transcription-coupled mim-catalysisREACT_811 (Reactome)
XAB2REACT_1584 (Reactome)
XPAArrowREACT_1311 (Reactome)
XPAREACT_1492 (Reactome)
XPC

HR23B

damaged DNA complex		REACT_1492 (Reactome)
XPC HR23B complexArrowREACT_1311 (Reactome)
XPC HR23B complexREACT_1987 (Reactome)
XPCREACT_1984 (Reactome)
dNTPREACT_1196 (Reactome)
dNTPREACT_353 (Reactome)
dNTPREACT_465 (Reactome)
dNTPREACT_677 (Reactome)
damaged DNA substrate nascent mRNA hybrid with 3' incisionArrowREACT_1274 (Reactome)
damaged DNA substrate nascent mRNA hybrid with 3' incisionREACT_811 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsArrowREACT_1196 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsArrowREACT_677 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsArrowREACT_811 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsREACT_1196 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsREACT_527 (Reactome)
damaged DNA substrate nascent mRNA hybrid with dual incisionsREACT_677 (Reactome)
damaged DNA substrate nascent mRNA hybridArrowREACT_1284 (Reactome)
damaged DNA substrate nascent mRNA hybridREACT_1274 (Reactome)
damaged DNA substrate nascent mRNA hybridREACT_1453 (Reactome)
damaged DNA substrateREACT_1987 (Reactome)
excised DNA fragment with lesionArrowREACT_1311 (Reactome)
excised DNA fragment with lesionArrowREACT_811 (Reactome)
incised DNA without lesionArrowREACT_1311 (Reactome)
incised DNA without lesionArrowREACT_353 (Reactome)
incised DNA without lesionArrowREACT_465 (Reactome)
incised DNA without lesionREACT_2181 (Reactome)
incised DNA without lesionREACT_353 (Reactome)
incised DNA without lesionREACT_465 (Reactome)
incision complex for GG-NERmim-catalysisREACT_1124 (Reactome)
newly synthesized DNA fragmentArrowREACT_1196 (Reactome)
newly synthesized DNA fragmentArrowREACT_353 (Reactome)
newly synthesized DNA fragmentArrowREACT_465 (Reactome)
newly synthesized DNA fragmentArrowREACT_677 (Reactome)
newly synthesized DNA fragmentREACT_2181 (Reactome)
newly synthesized DNA fragmentREACT_527 (Reactome)
pre-incision complex in GG-NERmim-catalysisREACT_1033 (Reactome)
pre-incision complex with open DNA bubbleREACT_2163 (Reactome)
repaired DNA template nascent mRNA hybridArrowREACT_527 (Reactome)
repaired DNA template nascent mRNA hybridREACT_551 (Reactome)
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