InterPro domain: IPR001044

This entry represents XPG (ERCC-5, also known as Rad2 in budding yeast, AtRAD2 or UVH3 in Arabidopsis and Rad13 in fission yeast), a single-stranded structure-specific DNA endonuclease, which cleaves single-stranded DNA during nucleotide excision repair to excise damaged DNA [ 1 ]. It makes the 3' incision in DNA nucleotide excision repair (NER); it binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble [ 2 , 3 ]. XPG is required for DNA replication fork maintenance and preservation of genomic stability [ 4 , 4 ]. It is involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site [ 5 ]. During HRR, binds to the replication fork with high specificity and stabilizes it [ 5 ] and upstream of HRR, it promotes the release of BRCA1 from DNA [ 5 ].

In Saccharomyces cerevisiae, Rad2 forms the Nucleotide Excision Repair Factor 3 (NEF3) complex with a subset of subunits of the transcription factor TFIIH [ 5 ]. Besides DNA damage repair, it is also required for efficient transcription [ 6 ].

Defects in XPG are the cause of xeroderma pigmentosum complementation group G (XP-G), which is an autosomal recessive pigmentary skin disorder characterised by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities [ 7 ].

1. Generation of DNA single-strand displacement by compromised nucleotide excision repair. EMBO J. 31, 3550-63
2. The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair. Nucleic Acids Res 48, 9943-9958
3. Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations. Proc Natl Acad Sci U S A 117, 14127-14138
4. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. Mol Cell 61, 535-546
5. Transcription factor TFIIH and DNA endonuclease Rad2 constitute yeast nucleotide excision repair factor 3: implications for nucleotide excision repair and Cockayne syndrome. Proc. Natl. Acad. Sci. U.S.A. 93, 10718-22
6. Requirement of yeast RAD2, a homolog of human XPG gene, for efficient RNA polymerase II transcription. implications for Cockayne syndrome. Cell 109, 823-34
7. Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient. Hum. Mol. Genet. 3, 963-7