2010 年 85 巻 1 号 p. 1-8
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 mec1Δ and mre11Δ 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, mec1Δ, tel1Δ, and mre11Δ strains. Thus, Mec1, Tel1, and Mre11 do not play roles in the point mutation response. We then found that the mec1Δ, mre11Δ, and mec1Δ tel1Δ 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 tel1Δ 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 mec1Δ, mre11Δ, or mec1Δ tel1Δ strain; however, it was detected in the wild-type and tel1Δ strains upon exposure to MMS. The elevated level of spontaneous LOH but not MMS-induced LOH in the mec1Δ, mre11Δ, and mec1Δ tel1Δ strains suggests the presence of high levels of spontaneous recombinogenic DNA damage, which differs from the damage induced by MMS treatment, in these strains.
