期刊
GENES & GENETIC SYSTEMS
卷 85, 期 1, 页码 1-8出版社
GENETICS SOC JAPAN
DOI: 10.1266/ggs.85.1
关键词
Saccharomyces cerevisiae; MEC1(ATR)/TEL1(ATM); spontaneous mutation; loss of heterozygosity; methylmethane sulfonate
资金
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
In eukaryotes, together with the Mre11/Rad50/Xrs2 (or Nbs1) complex, a family of related protein kinases (the ATM family) is involved in checkpoint activation in response to DNA double-strand breaks. In Saccharomyces cerevisiae, two members of this family, MEC1 and TEL1, have functionally redundant roles in DNA damage repair. Strains with mutations in their mec1 as well as mre11 genes are very sensitive to DNA damaging agents, show defective induction of damage-induced cell-cycle checkpoints, and defective damage-induced homologous recombination. However, the fact that both the mec1 Delta and mre11 Delta strains exhibit the spontaneous hyper-recombination phenotype is paradoxical in light of the homologous recombination defects in these strains. In this study, we constructed yeast mec1, tel1, and mre11 null mutations and characterized their genome stability properties. Spontaneous and methylmethane sulfonate (MMS)-induced point mutations, base-substitutions, and frameshifts occurred to an almost equal extent in the wild-type, mec1 Delta, tel1 Delta, and mre11 Delta strains. Thus, Mec1, Tel1, and Mre11 do not play roles in the point mutation response. We then found that the mec1 Delta, mre11 Delta, and mec1 Delta tel1 Delta strains demonstrated increased rates of spontaneous loss of heterozygosity (LOH), which includes crossover, gene conversion, and chromosome loss, compared with the wild-type strain. In the tel1 Delta strain, the rate of spontaneous LOH was as low as that in the wild-type strain. Finally, no induction of LOH by MMS was observed in the mec1 Delta, mre11 Delta, or mec1 Delta tel1 Delta strain; however, it was detected in the wild-type and tel1 Delta strains upon exposure to MMS. The elevated level of spontaneous LOH but not MMS-induced LOH in the mec1 Delta, mre11 Delta, and mec1 Delta tel1 Delta strains suggests the presence of high levels of spontaneous recombinogenic DNA damage, which differs from the damage induced by MMS treatment, in these strains.
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