Xeroderma pigmentosum (XP)  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
XPG belongs to a family of proteins [2,3,4,5,6] that are composed of two
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 .
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
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.
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
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.
O'Donovan A. Davies A.A. Moggs J.G. West S.C. Wood R.D.
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