Family

RAD3/XPD family (IPR001945)

Short name: RAD3/XPD

Family relationships

Description

Xeroderma pigmentosum (XP) [PMID: 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 [PMID: 8464724, PMID: 8206890]. XP-G can be corrected by a 133 Kd nuclear protein, XPGC [PMID: 8160271]. XPGC is an acidic protein that confers normal UV resistance in expressing cells [PMID: 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 [PMID: 8206890, PMID: 8090225]. XPGC cleaves one strand of the duplex at the border with the single-stranded region [PMID: 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 [PMID: 8090225, PMID: 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.

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 [PMID: 9101292, PMID: 7920640]. 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 [PMID: 7920640].

XPD belongs to a family of ATP-dependent helicases that are characterised by a 'D-E-A-H' motif [PMID: 1956796]. 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.

GO terms

Biological Process

GO:0006289 nucleotide-excision repair

Molecular Function

GO:0005524 ATP binding
GO:0004003 ATP-dependent DNA helicase activity
GO:0003677 DNA binding
GO:0016818 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides

Cellular Component

GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER
PRINTS