title: The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.
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.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Masutani
authors.forename: R
authors.initials: R
authors.lastname: Kusumoto
authors.forename: A
authors.initials: A
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Dohmae
authors.forename: M
authors.initials: M
authors.lastname: Yokoi
authors.forename: M
authors.initials: M
authors.lastname: Yuasa
authors.forename: M
authors.initials: M
authors.lastname: Araki
authors.forename: S
authors.initials: S
authors.lastname: Iwai
authors.forename: K
authors.initials: K
authors.lastname: Takio
authors.forename: F
authors.initials: F
authors.lastname: Hanaoka
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D003001:Cloning, Molecular; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D011994:Recombinant Proteins; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases