Xeroderma pigmentosum (XP) [1] is a human autosomal recessive disease, characterized 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. The defect in XP-G can be corrected by a 133 Kd nuclear protein called XPG (or XPGC) [2].

XPG belongs to a family of proteins [2,3,4,5,6] that are composed of two main subsets:

• Subset 1, to which belongs XPG, RAD2 from budding yeast and rad13 from fission yeast. RAD2 and XPG are single-stranded DNA endonucleases [7,8]. XPG makes the 3'incision in human DNA nucleotide excision repair [9].
• Subset 2, to which belongs mouse and human FEN-1, rad2 from fission yeast, and RAD27 from budding yeast. FEN-1 is a structure-specific endonuclease.

In addition to the proteins listed in the above groups, this family also includes:

• Fission yeast exo1, a 5'->3' double-stranded DNA exonuclease that could act in a pathway that corrects mismatched base pairs.
• Yeast EXO1 (DHS1), a protein with probably the same function as exo1.
• 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; indeed, they are largely absent from proteins belonging to the second subset.

We have developed two signature patterns for these proteins. The first corresponds to the central part of the N-region, the second to part of the I-region and includes the putative catalytic core pentapeptide.