41. Disruption of Xpg Increases Spontaneous Mutation Frequency, Particularly A:T to-C:G Transversion

Tadahiro Shiomi, Naoko Shiomi, Emiko Hayashi*, Shun-ichi Sasanuma and Kazuei Mita
(*Chiba University)

Keywords: xeroderma pigmentosum, Xpg, supF, mutation assay, transversion

Cells isolated from Xpg (the mouse counterpart of human XPG)-deficient 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 the nucleotide excision repair (NER) protein, was involved in repair of oxidative base such as thymine glycol and 8-oxo-guanine, 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.

Publications:
Shiomi, N., Hayashi, E., Sasanuma, S., Mita, K., Shiomi, T.: Mutat.Res., 487, 127-135, 2001.