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

Nature. 1999 Jun 17;399(6737):700-4. doi: 10.1038/21447.

Abstract

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. 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. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta. This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell-Free System
  • Cloning, Molecular
  • DNA Repair
  • DNA-Directed DNA Polymerase / genetics*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Sequence Homology, Amino Acid
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics*

Substances

  • Recombinant Proteins
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • Rad30 protein

Associated data

  • GENBANK/AB024313