The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η

Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers, Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA(1,2). It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis; but the gene product has never been isolated Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts(3). Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta (ref. 4). This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins(5-10) which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together these results indicate that DNA polymerase eta could be the XPV gene product.