The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.
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.
Masutani
C
C
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Kusumoto
R
R
Yamada
A
A
Dohmae
N
N
Yokoi
M
M
Yuasa
M
M
Araki
M
M
Iwai
S
S
Takio
K
K
Hanaoka
F
F
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
D004259:DNA-Directed DNA Polymerase; D011994:Recombinant Proteins; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases