Nucleotide excision repair in xeroderma pigmentosum (Homo sapiens)

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1325153251818314, 16221158, 27Recognition of UV-damangedDNA blocks RNA polymerase and serves as a damage recognitioin signal The choice of NER DNA ligase depends on the DNA polymerase involved in repair synthesis and probably the stage of the cell cycle (Moser et al. 2007).DNA lesionUV-damaged DNA Excised nucleotidesTranscription factor II H (TFIIH)DNA unwinding by XPB and XPD helicasesStep 1 - Recognition of damaged DNAXPC complexUVRorStep 4 - gap-filling DNA synthesis and ligationEarly chromatin remodelingTranscription-coupled repairTCR-initiation complexUV-DDBLegend:UV - RadiationDNAMutated XP geneNucleotide lesionStimulation UbiquitylationDNA damage signalingInhibition of UV-DDB when no UV-damage is present.With UV damage, inhibition is lifted RPA1023256RPA2LIG1p52/GTF2H4XPAXAB2POLHPOLD1TTDA/GTF2H5UVSSAHistone H2ACHD1L (ALC1)RNA polymerase IITFIISLIG3HMGN1PARP1Histone H4POLKSLX4IPERCC6 (CSB)CSN (COP9)CSBXRCC1Histone H3RAD23BXRCC1RAD18XPAUSP7RPA1SLX4RPA371121287231012, 172, 8, 1220RBX1CUL4ACUL4BERCC8 (CSA)DDB1CDK7 MNAT1CCNHXPD/ERCC2XPB/ERCC3p62/GTF2H1p44/GTF2H2p34 /GTF2H3XPF/ERCC1XPG/ERCC4Step 3 - Incision and excision24POLD2POLD3POLD4POLEPOLE2POLE3POLE4PCNARFC1RFC2RFC3RFC4RFC5LigationGlobal genome repairXPE complexRBX1CUL4A4CUL4BXPE (DDB2)8DDB1XPCRAD23A (?)CETN2 (Centrin 2)9RPARPA3RPA2RPA1in non-replicating cellsin replicating cellsCSN (COP9)23XPD/ERCC2XPB/ERCC3RPARPA3RPA2RPA1Step 2 - DNA binding and unwinding1


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, which is subsequently filled in by DNA polymerase, which uses the undamaged strand as a template. NER can be divided into two subpathways (Global 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's 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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History

View all...
CompareRevisionActionTimeUserComment
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
BRCA1GeneProductENSG00000012048 (Ensembl)
CCNHGeneProductENSG00000134480 (Ensembl)
CDK7 GeneProductENSG00000134058 (Ensembl) This subcomplex dissociates after XPA binds
CETN2 (Centrin 2)GeneProductENSG00000147400 (Ensembl) "CENTRIN 2 enhances the affinity of XPC/RAD23B for DNA distortions"
CHD1L (ALC1)GeneProductENSG00000131778 (Ensembl)
CSBGeneProduct
CSN (COP9)ProteinA0A096LP07 (Uniprot-TrEMBL)
CUL4AGeneProductENSG00000139842 (Ensembl)
CUL4BGeneProductENSG00000158290 (Ensembl)
DDB1GeneProductENSG00000167986 (Ensembl)
ERCC6 (CSB) GeneProductENSG00000225830 (Ensembl) https://reactome.org/PathwayBrowser/#/R-HSA-5696398&SEL=R-HSA-6781823&PATH=R-HSA-73894
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)
RAD23A (?)GeneProductENSG00000179262 (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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