Nucleotide excision repair in xeroderma pigmentosum (Homo sapiens)

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210, 251226151, 14113029151265114RPAThe choice of DNA ligase depends on the DNA polymerase involved in repair synthesis and probably the stage of the cell cycle (Moser et al. 2007).DNA damage signalingXPC complexDNA lesionTranscription-coupled repairUVRInhibition of UV-DDB when no UV-damage is present.With UV damage, inhibition is lifted UV-damaged DNA DNA polymerasesEarly chromatin remodelingStep 4 - Gap-filling, DNA synthesis and ligationTCR-initiation complexLegend:UV - RadiationDNAMutated XP geneNucleotide lesionStimulation UbiquitylationTranscription factor II H (TFIIH)DNA unwinding by XPB and XPD helicasesUV-DDBorStep 1 - Recognition of damaged DNA112024ERCC6UVSSAPARP1BRCA1RAD23BERCC6 (CSB)XRCC1BRCA1Histone H2AXAB2RAD18XRCC1SLX4HMGN1TTDA/GTF2H5RPA3SLX4IPCHD1L (ALC1)RPA2XPACSN (COP9)RNA polymerase IITFIISUSP7RPA1XPALIG1POLD1POLKp52/GTF2H4LIG3Histone H4POLHHistone H31938, 1714, 17, 2622207286271313RBX1CUL4ACUL4BERCC8 (CSA)DDB1CDK7 MNAT1CCNHXPD/ERCC2XPB/ERCC3p62/GTF2H1p44/GTF2H2p34 /GTF2H3XPF/ERCC1XPG/ERCC416Step 3 - Incision and excisionPOLD2POLD3POLD4POLEPOLE2POLE3POLE4PCNARFC1RFC2RFC3RFC4RFC5LigationGlobal genome repairXPE complexRBX1CUL4ACUL4B9XPE (DDB2)DDB114XPCRAD23ACETN218RPARPA3RPA2RPA1In non-replicating cellsIn replicating cellsCSN (COP9)20XPD/ERCC2XPB/ERCC3RPARPA3RPA2RPA129Step 2 - DNA binding and unwinding


Description

Nucleotide excision repair is a DNA repair mechanism that repairs DNA damaged by UV radiation. This type of damage produces bulky distortions in the shape of DNA double helix due to the addition of DNA adducts, mostly thymine dimers and 6,4-photoproducts.

Recognition of distortions leads to the removal of a short single-stranded DNA segment that includes the lesion, creating a single-strand gap in the DNA. That is subsequently filled in by DNA polymerase, which uses the undamaged strand as a template. NER can be divided into two subpathways (blobal genomic NER and transcription coupled NER) that differ only in their recognition of helix-distorting DNA damage. Nucleotide excision repair has more complexity in eukaryotes.

Nucleotide excision repair (NER) is a particularly important DNA repair mechanism as evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins including xeroderma pigmentosum and Cockayne syndrome.

This pathway was adapted from KEGG, REPAIRtoire and Wikipedia. The pathway layout is based on KEGG.

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Bibliography

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  13. Thakar T, Leung W, Nicolae CM, Clements KE, Shen B, Bielinsky AK, Moldovan GL; ''Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly.''; Nat Commun, 2020 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
135241view22:54, 8 August 2024EweitzClear cache to update board dimensions
135240view22:53, 8 August 2024EweitzRefine case, paragraph positioning
135239view22:46, 8 August 2024EweitzEconomize layout
134573view23:31, 22 July 2024EweitzOntology Term : 'Cockayne syndrome' added !
134572view23:31, 22 July 2024EweitzModified description
134492view05:25, 22 July 2024EgonwRemoved template comments
134133view13:30, 30 June 2024EgonwConverted a label to a pathway datanode
119169view16:21, 19 June 2021NataliehCorrected a mistake
119168view16:20, 19 June 2021NataliehDeleted an unwanted node
119167view16:19, 19 June 2021NataliehMarked XP mutations
119166view15:53, 19 June 2021NataliehAdded missing links between some nodes
118858view12:07, 2 June 2021NataliehDeleted an unwanted node
118855view11:34, 2 June 2021FehrhartOntology Term : 'xeroderma pigmentosum' added !
118854view11:33, 2 June 2021FehrhartModified title
118781view16:50, 1 June 2021NataliehModified title
118767view15:30, 1 June 2021Natalieh
118766view15:30, 1 June 2021Natalieh
118765view15:25, 1 June 2021NataliehNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
BRCA1GeneProductBRCA1 (HGNC)
BRCA1GeneProductENSG00000012048 (Ensembl)
CCNHGeneProductENSG00000134480 (Ensembl)
CDK7 GeneProductENSG00000134058 (Ensembl) This subcomplex dissociates after XPA binds
CETN2GeneProductENSG00000147400 (Ensembl) "CENTRIN 2 enhances the affinity of XPC/RAD23B for DNA distortions"
CHD1L (ALC1)GeneProductENSG00000131778 (Ensembl)
CSN (COP9)ProteinA0A096LP07 (Uniprot-TrEMBL)
CUL4AGeneProductENSG00000139842 (Ensembl)
CUL4BGeneProductENSG00000158290 (Ensembl)
DDB1GeneProductENSG00000167986 (Ensembl)
DNA damage signalingPathway
ERCC6 (CSB) GeneProductENSG00000225830 (Ensembl) https://reactome.org/PathwayBrowser/#/R-HSA-5696398&SEL=R-HSA-6781823&PATH=R-HSA-73894
ERCC6GeneProductENSG00000225830 (Ensembl)
ERCC8 (CSA)GeneProductENSG00000049167 (Ensembl)
HMGN1GeneProductENSG00000205581 (Ensembl)
Histone H2AProteinA0A024R017 (Uniprot-TrEMBL)
Histone H3ProteinB2R4P9 (Uniprot-TrEMBL)
Histone H4ProteinB2R4R0 (Uniprot-TrEMBL)
LIG1GeneProductENSG00000105486 (Ensembl)
LIG3GeneProductENSG00000005156 (Ensembl)
MNAT1GeneProductENSG00000020426 (Ensembl)
PARP1GeneProductPARP1 (HGNC)
PCNAGeneProductENSG00000132646 (Ensembl)
POLD1GeneProductENSG00000062822 (Ensembl)
POLD2GeneProductENSG00000106628 (Ensembl)
POLD3GeneProductENSG00000077514 (Ensembl) DNA polymerase delta
POLD4GeneProductENSG00000175482 (Ensembl)
POLE2GeneProductENSG00000100479 (Ensembl)
POLE3GeneProductENSG00000148229 (Ensembl)
POLE4GeneProductENSG00000115350 (Ensembl)
POLEGeneProductENSG00000177084 (Ensembl)
POLHGeneProductENSG00000170734 (Ensembl) DNA polymerase eta
POLKGeneProductENSG00000122008 (Ensembl) DNA polymerase kappa
RAD18GeneProductRAD18 (HGNC)
RAD23AGeneProductENSG00000179262 (Ensembl)
RAD23BGeneProductENSG00000119318 (Ensembl)
RBX1GeneProductENSG00000100387 (Ensembl)
RFC1GeneProductENSG00000035928 (Ensembl)
RFC2GeneProductENSG00000049541 (Ensembl)
RFC3GeneProductENSG00000133119 (Ensembl)
RFC4GeneProductENSG00000163918 (Ensembl)
RFC5GeneProductENSG00000111445 (Ensembl)
RNA polymerase IIProtein
RPA1GeneProductENSG00000132383 (Ensembl)
RPA2GeneProductENSG00000117748 (Ensembl)
RPA3GeneProductENSG00000106399 (Ensembl)
SLX4GeneProductENSG00000188827 (Ensembl)
SLX4IPGeneProductENSG00000149346 (Ensembl)
TFIISGeneProduct
TTDA/GTF2H5GeneProductENSG00000272047 (Ensembl)
USP7GeneProductENSG00000187555 (Ensembl)
UVSSAGeneProductENSG00000163945 (Ensembl)
XAB2GeneProductENSG00000076924 (Ensembl)
XPAGeneProductENSG00000136936 (Ensembl)
XPB/ERCC3GeneProductENSG00000163161 (Ensembl)
XPCGeneProductENSG00000154767 (Ensembl)
XPD/ERCC2GeneProductENSG00000104884 (Ensembl)
XPE (DDB2)GeneProductENSG00000134574 (Ensembl) Structural analysis revealed that DDB2 interacts extensively with DNA containing a lesion, while DDB1 stabilizes DDB2 but does not bind to DNA. DDB2 unwinds and kinks the DNA, and the lesion is consequently flipped out and partially held in a shallow binding pocket of DDB2
XPF/ERCC1GeneProductENSG00000012061 (Ensembl)
XPG/ERCC4GeneProductENSG00000175595 (Ensembl)
XRCC1GeneProductENSG00000073050 (Ensembl)
p34 /GTF2H3GeneProductENSG00000111358 (Ensembl)
p44/GTF2H2GeneProductENSG00000145736 (Ensembl)
p52/GTF2H4GeneProductENSG00000213780 (Ensembl)
p62/GTF2H1GeneProductENSG00000110768 (Ensembl)

Annotated Interactions

No annotated interactions

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