Nucleotide Excision Repair (Homo sapiens)

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1-3877875, 6nucleoplasmdamaged DNA substrateDNA polymerase epsilonStalled Pol II complex with damaged DNA hybriddNTPDNA ligase IXPC:HR23B complexdNTPDNA Polymerase delta tetramerTFIIHincised DNA without lesionERCC1, DNA excision repair proteinrepaired DNA template:nascent mRNA hybriddNTPRPA heterotrimerdamaged DNA substrate:nascent mRNA hybrid with dual incisionsStalled Pol II in TC-NERXPA-binding protein 2TFIIS proteinIncision complex with 3'-incised damaged DNApre-incision complex with open DNA bubbleincision complex for GG-NERincised DNA without lesionDDB1, DNA damage binding protein 1XPC:HR23B:damaged DNA complexActive Pol II complex with repaired DNA template:mRNA hybridnewly synthesized DNA fragmentnewly synthesized DNA fragmentnewly synthesized DNA fragmentHR23B, RAD23B homolog proteindamaged DNA substrate:nascent mRNA hybriddNTPPCNA homotrimerTranscription-coupled (TC) repair complexnewly synthesized DNA fragmentincised DNA without lesionnewly synthesized DNA fragmentexcised DNA fragment with lesionERCC1:XPF complexRepaired double-stranded DNADNA Polymerase delta tetramerXPC proteinRNA Polymerase II holoenzyme complex (hyperphosphorylated)CSA proteindamaged DNA substrate:nascent mRNA hybrid with 3' incisionDDB2, DNA damage binding protein 2XPG proteinActive Pol II transcription complex with damaged DNA hybridRFC Heteropentamerincised DNA without lesionXPA proteinnewly synthesized DNA fragmentCSB proteinpre-incision complex in GG-NERXPF protein4


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.

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  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
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  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

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113472view11:54, 2 November 2020ReactomeTeamReactome version 74
112671view16:06, 9 October 2020ReactomeTeamReactome version 73
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93777view13:35, 16 August 2017ReactomeTeamreactome version 61
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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 hybrid

ComplexREACT_3609 (Reactome)
Active Pol II complex

with repaired DNA template:mRNA hybrid

ComplexREACT_2462 (Reactome)
CSA protein ProteinQ13216 (UniProt)
CSB protein ProteinQ03468 (UniProt)
DDB1, DNA damage

binding protein 1

ProteinQ16531 (UniProt)
DDB2, DNA

damage binding protein 2

ProteinQ92466 (UniProt)
DNA Polymerase

delta tetramer

ComplexREACT_5801 (Reactome)
DNA ligase I ProteinP18858 (UniProt)
DNA polymerase

epsilon

ComplexREACT_4621 (Reactome)
ERCC1, DNA excision

repair protein

ProteinP07992 (UniProt)
ERCC1:XPF

complex

ComplexREACT_3454 (Reactome)
HR23B, RAD23B

homolog protein

ProteinP54727 (UniProt)
Incision

complex with 3'-incised damaged DNA

ComplexREACT_5099 (Reactome)
PCNA homotrimer ComplexREACT_2542 (Reactome)
RFC Heteropentamer ComplexREACT_4881 (Reactome)
RNA Polymerase II

holoenzyme complex (hyperphosphorylat ed)

ComplexREACT_4889 (Reactome)
RPA heterotrimer ComplexREACT_3427 (Reactome)
Repaired double-

stranded DNA

UnknownREACT_4318 (Reactome)
Stalled Pol II

complex with damaged DNA hybrid

ComplexREACT_3072 (Reactome)
Stalled Pol II in TC-

NER

ComplexREACT_4443 (Reactome)
TFIIH ComplexREACT_3832 (Reactome)
TFIIS protein ProteinP23193 (UniProt)
Transcription-

coupled (TC) repair complex

ComplexREACT_3969 (Reactome)
XPA protein ProteinP23025 (UniProt)
XPA-binding

protein 2

ProteinQ9HCS7 (UniProt)
XPC protein ProteinQ01831 (UniProt)
XPC:HR23B

complex

ComplexREACT_4017 (Reactome)
XPC:HR23B:

damaged DNA complex

ComplexREACT_3245 (Reactome)
XPF

protein

ProteinQ92889 (UniProt)
XPG protein ProteinP28715 (UniProt)
dNTP UnknownREACT_2960 (Reactome)
damaged DNA

substrate

UnknownREACT_2765 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid

UnknownREACT_3022 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with 3' incision

UnknownREACT_2845 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with dual incisions

UnknownREACT_5428 (Reactome)
excised DNA

fragment with lesion

UnknownREACT_2556 (Reactome)
incised DNA

without lesion

UnknownREACT_3852 (Reactome)
incised DNA without

lesion

UnknownREACT_3852 (Reactome)
incision complex for

GG-NER

ComplexREACT_5159 (Reactome)
newly synthesized

DNA fragment

UnknownREACT_3448 (Reactome)
pre-incision

complex with open DNA bubble

ComplexREACT_5689 (Reactome)
pre-incision complex

in GG-NER

ComplexREACT_5795 (Reactome)
repaired DNA

template:nascent mRNA hybrid

UnknownREACT_5433 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1980"
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