RRC ID |
62080
|
著者 |
Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F.
|
タイトル |
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.
|
ジャーナル |
Nature
|
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.
|
巻・号 |
399(6737)
|
ページ |
700-4
|
公開日 |
1999-6-17
|
DOI |
10.1038/21447
|
PMID |
10385124
|
MeSH |
Alleles
Amino Acid Sequence
Animals
Cell Line
Cell-Free System
Cloning, Molecular
DNA Polymerase iota
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*
|
IF |
42.779
|
リソース情報 |
ヒト・動物細胞 |
NB1RGB(RCB0222) |