Disruption of Xpg increases spontaneous mutation frequency, particularly A:T to C:G transversion.
Cells isolated from Xpg (the mouse counterpart of XPG)-disrupted mice underwent premature senescence and showed early onset of immortalization, suggesting that Xpg might be involved in genetic stability. Recent studies showed that human XPG, in addition to its function in the nucleotide excision repair (NER), was involved in the repair of oxidative base damages such as thymine glycol (Tg) and 8-oxo-guanine (8-oxoG), and this may explain the genetic instability observed in Xpg-deficient cells. To clarify this point, we determined spontaneous mutation frequencies and the type of spontaneous base substitution mutations in cells obtained from normal and Xpg-deficient mice using the supF shuttle vector (pNY200) for mutation assay. The spontaneous mutation frequency of the supF gene in pNY200 propagated in the Xpg-deficient cells was about three times higher than that in normal cells, indicating the importance of Xpg in reducing the frequency of spontaneous mutations. The frequency of spontaneous base substitution mutations at A:T sites, particularly that of the A:T to C:G transversion, increased markedly in the Xpg-deficient cells.
Shiomi
N
N
The Genome Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Hayashi
E
E
Sasanuma
S
S
Mita
K
K
Shiomi
T
T
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004720:Endonucleases; D005347:Fibroblasts; D016368:Frameshift Mutation; D016153:Genes, Suppressor; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense; D009687:Nuclear Proteins; D017354:Point Mutation; D012329:RNA, Bacterial / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion; D014157:Transcription Factors; D014162:Transfection; D000099250:DNA Excision Repair Protein ERCC-5
D004268:DNA-Binding Proteins; D004720:Endonucleases; D006147:Guanine; D009687:Nuclear Proteins; D012329:RNA, Bacterial; D012343:RNA, Transfer; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C096275:supF tRNA; C024829:8-hydroxyguanine