Xeroderma pigmentosum (XP) [ (PUBMED:8160271) ] is a human autosomal recessive disease, characterised by a high incidence of sunlight-induced skin cancer. People's skin cells with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-G is one of the most rare and phenotypically heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA excision repair [ (PUBMED:8464724) (PUBMED:8206890) ]. XP-G can be corrected by a 133 Kd nuclear protein, XPGC [ (PUBMED:8160271) ]. XPGC is an acidic protein that confers normal UV resistance in expressing cells [ (PUBMED:8206890) ]. It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms [ (PUBMED:8206890) (PUBMED:8090225) ]. XPGC cleaves one strand of the duplex at the border with the single-stranded region [ (PUBMED:8090225) ].
XPG belongs to a family of proteins that includes RAD2 from Saccharomyces cerevisiae (Baker's yeast) and rad13 from Schizosaccharomyces pombe (Fission yeast), which are single-stranded DNA endonucleases [ (PUBMED:8090225) (PUBMED:8247134) ]; mouse and human FEN-1, a structure-specific endonuclease; RAD2 from fission yeast and RAD27 from budding yeast; fission yeast exo1, a 5'-3' double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, and yeast DIN7. Sequence alignment of this family of proteins reveals that similarities are largely confined to two regions. The first is located at the N-terminal extremity (N-region) and corresponds to the first 95 to 105 amino acids. The second region is internal (I-region) and found towards the C terminus; it spans about 140 residues and contains a highly conserved core of 27 amino acids that includes a conserved pentapeptide (E-A-[DE]-A-[QS]). It is possible that the conserved acidic residues are involved in the catalytic mechanism of DNA excision repair in XPG. The amino acids linking the N- and I-regions are not conserved.
Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G.
Science. 1997; 275: 990-3
Display abstract
In normal human cells, damage due to ultraviolet light is preferentially removed from active genes by nucleotide excision repair (NER) in a transcription-coupled repair (TCR) process that requires the gene products defective in Cockayne syndrome (CS). Oxidative damage, including thymine glycols, is shown to be removed by TCR in cells from normal individuals and from xeroderma pigmentosum (XP)-A, XP-F, and XP-G patients who have NER defects but not from XP-G patients who have severe CS. Thus, TCR of oxidative damage requires an XPG function distinct from its NER endonuclease activity. These results raise the possibility that defective TCR of oxidative damage contributes to the developmental defects associated with CS.
Xeroderma pigmentosum and nucleotide excision repair of DNA.
Trends Biochem Sci. 1994; 19: 83-6
Display abstract
Nucleotide excision repair is a versatile strategy for removing DNA damage from the genome. Tremendous progress in understanding this process has been made in the last few years, and the field continues to develop rapidly. Exciting connections have emerged between nucleotide excision repair, transcription, and DNA replication, but many mysteries remain concerning the biochemical details of the mechanism, the connection with several human inherited syndromes, and the role of DNA repair in preventing cancer.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with XPGN domain which could be assigned to a KEGG orthologous group, and not all proteins containing XPGN domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
