Nucleotide Excision Repair (Homo sapiens)

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2, 4, 813116, 73nucleoplasmXPC proteinexcised DNA fragment with lesionRNA Polymerase II holoenzyme complex (hyperphosphorylated)repaired DNA template:nascent mRNA hybridnewly synthesized DNA fragmentPCNA homotrimerdNTPXPA proteinincised DNA without lesionincised DNA without lesiondNTPdamaged DNA substrate:nascent mRNA hybrid with dual incisionsdamaged DNA substrateStalled Pol II in TC-NERTFIIS proteinActive Pol II transcription complex with damaged DNA hybridCSB proteinERCC1:XPF complexTFIIHpre-incision complex with open DNA bubblenewly synthesized DNA fragmentXPG proteinXPC:HR23B complexDNA Polymerase delta tetramernewly synthesized DNA fragmentnewly synthesized DNA fragmentdNTPDNA ligase IHR23B, RAD23B homolog proteindamaged DNA substrate:nascent mRNA hybrid with 3' incisionincised DNA without lesionCSA proteinActive Pol II complex with repaired DNA template:mRNA hybridincision complex for GG-NERdNTPIncision complex with 3'-incised damaged DNApre-incision complex in GG-NERDNA Polymerase delta tetramerRFC HeteropentamerERCC1, DNA excision repair proteinRepaired double-stranded DNAXPA-binding protein 2Transcription-coupled (TC) repair complexXPC:HR23B:damaged DNA complexRPA heterotrimerdamaged DNA substrate:nascent mRNA hybridDNA polymerase epsilonnewly synthesized DNA fragmentDDB2, DNA damage binding protein 2XPF proteinnewly synthesized DNA fragmentStalled Pol II complex with damaged DNA hybridDDB1, DNA damage binding protein 1incised DNA without lesion5


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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  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
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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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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

REACT_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 REACT_2960 (Reactome)
damaged DNA

substrate

REACT_2765 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid

REACT_3022 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with 3' incision

REACT_2845 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with dual incisions

REACT_5428 (Reactome)
excised DNA

fragment with lesion

REACT_2556 (Reactome)
incised DNA

without lesion

REACT_3852 (Reactome)
incised DNA without

lesion

REACT_3852 (Reactome)
incision complex for

GG-NER

ComplexREACT_5159 (Reactome)
newly synthesized

DNA fragment

REACT_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

REACT_5433 (Reactome)

Annotated Interactions

No annotated interactions

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