ERCC5

ERCC5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5EKF, 5EKG
Identifiers
Aliases	ERCC5, COFS3, ERCM2, UVDR, XPG, XPGC, ERCC5-201, excision repair cross-complementation group 5, ERCC excision repair 5, endonuclease
External IDs	OMIM: 133530; MGI: 103582; HomoloGene: 133551; GeneCards: ERCC5; OMA:ERCC5 - orthologs
Gene location (Human)
Chr.	Chromosome 13 (human)
End	102,875,995 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	44,220,420 bp
RNA expression pattern
	Top expressed in
	granulocyte; ; Achilles tendon; ; body of pancreas; ; skin of leg; ; skin of abdomen; ; right lobe of liver; ; anterior pituitary; ; right lung; ; mucosa of transverse colon; ; tibial nerve;
	Top expressed in
	Rostral migratory stream; ; genital tubercle; ; tail of embryo; ; stroma of bone marrow; ; ganglionic eminence; ; ventricular zone; ; neural layer of retina; ; corneal stroma; ; ciliary body; ; supraoptic nucleus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding; protein homodimerization activity; hydrolase activity, acting on ester bonds; protein N-terminus binding; bubble DNA binding; metal ion binding; single-stranded DNA binding; protein binding; catalytic activity; nuclease activity; endonuclease activity; double-stranded DNA binding; endodeoxyribonuclease activity; hydrolase activity; RNA polymerase II complex binding; protein-containing complex binding;
Cellular component	RNA polymerase II, holoenzyme; transcription factor TFIIH holo complex; DNA replication factor A complex; nucleus; nucleoplasm; nucleotide-excision repair complex;
Biological process	negative regulation of apoptotic process; cellular response to DNA damage stimulus; UV protection; transcription-coupled nucleotide-excision repair; nucleotide-excision repair, DNA incision; response to UV; response to UV-C; nucleotide-excision repair; nucleotide-excision repair, preincision complex stabilization; DNA repair; nucleotide-excision repair, preincision complex assembly; nucleotide-excision repair, DNA incision, 5'-to lesion; nucleotide-excision repair, DNA incision, 3'-to lesion;
	Sources:Amigo / QuickGO
Orthologs
	2073
	22592
	ENSG00000134899
	ENSMUSG00000026048
	P28715
	P35689
	NM_000123
	NM_011729
	NP_000114
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.^[5]^[6]

Function

Excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G) is involved in excision repair of UV-induced DNA damage. Mutations cause Cockayne syndrome, which is characterized by severe growth defects, mental retardation, and cachexia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been described, but the biological validity of all variants has not been determined.^[6]

Mutations in ERCC5 cause arthrogryposis.^[7]

XPG is a structure specific endonuclease that incises DNA at the 3’ side of the damaged nucleotide during nucleotide excision repair.

Syndromes

Mutational defects in the Ercc5(Xpg) gene can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or in combination with the severe neurodevelopmental disorder Cockayne syndrome (CS) or the infantile lethal cerebro-oculo-facio-skeletal syndrome.^[8]

Mouse model

An Ercc5(Xpg) mutant mouse model presented features of premature aging including cachexia and osteoporosis with pronounced degenerative phenotypes in both liver and brain.^[8] These mutant mice developed a multi-system premature aging degenerative phenotype that appears to strengthen the link between DNA damage and aging.^[8] (see DNA damage theory of aging).

Dietary restriction, which extends lifespan of wild-type mice, also substantially increased the lifespan of Ercc5(Xpg) mutant mice.^[9] Dietary restriction of the mutant mice, while delaying aging, also appeared to slow the accumulation of genome wide DNA damage and to preserve transcriptional output, thus contributing to improved cell viability.

Interactions

ERCC5 has been shown to interact with ERCC2.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134899 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026048 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Samec S, Jones TA, Corlet J, Scherly D, Sheer D, Wood RD, Clarkson SG (May 1994). "The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization". Genomics. 21 (1): 283–5. doi:10.1006/geno.1994.1261. PMID 8088806.
^ ^a ^b "Entrez Gene: ERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))".
^ Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH (July 2014). "A novel homozygous ERCC5 truncating mutation in a family with prenatal arthrogryposis--further evidence of genotype-phenotype correlation". American Journal of Medical Genetics. Part A. 164A (7): 1777–83. doi:10.1002/ajmg.a.36506. PMID 24700531. S2CID 8023991.
^ ^a ^b ^c Barnhoorn S, Uittenboogaard LM, Jaarsma D, Vermeij WP, Tresini M, Weymaere M, Menoni H, Brandt RM, de Waard MC, Botter SM, Sarker AH, Jaspers NG, van der Horst GT, Cooper PK, Hoeijmakers JH, van der Pluijm I (October 2014). "Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency". PLOS Genetics. 10 (10): e1004686. doi:10.1371/journal.pgen.1004686. PMC 4191938. PMID 25299392.
^ Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH (September 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC 5161687. PMID 27556946.
^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (February 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.