| Type: | Family | Name: | Xeroderma pigmentosum group D protein |
| Description: | Xeroderma pigmentosum (XP) [] 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 [, ]. XP-G can be corrected by a 133 Kd nuclear protein, XPGC []. XPGC is an acidic protein that confers normal UV resistance in expressing cells []. 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 [, ]. XPGC cleaves one strand of the duplex at the border with the single-stranded region [].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 [, ]; 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.The XP group D gene product (XPD) is a helicase that is required for nucleotide excision repair, and is also one of the components of basal transcription factor TFIIH [, ]. DNA repair defects in the XPD group are associated with the clinical features of XP and trichothiodystrophy (TTD), which is characterised by sulphur-deficient brittle hair and a variety of other associated abnormalities, but no skin cancer [].XPD belongs to a family of ATP-dependent helicases that are characterised by a 'D-E-A-H' motif []. This resembles the 'D-E-A-D-box' of other known helicases, which represents a special version of the B motif of ATP-binding proteins. In XPD, His replaces the second Asp. | Short Name: | XPGD_DNA_repair |
| GO Term | Gene Name |
|---|---|
| GO:0003677 | IPR001945 |
| GO:0004003 | IPR001945 |
| GO:0005524 | IPR001945 |
| GO:0016818 | IPR001945 |
| GO:0006289 | IPR001945 |
| GO:0005634 | IPR001945 |
| GO Term | Gene Name |
|---|---|
| GO:0003677 | IPR001945 |
| GO:0004003 | IPR001945 |
| GO:0005524 | IPR001945 |
| GO:0016818 | IPR001945 |
| GO:0006289 | IPR001945 |
| GO:0005634 | IPR001945 |
