RAD9, RAD17, and RAD24 Are Required for S Phase Regulation in Saccharomyces cerevisiae in Response to DNA Damage

[摘要] We have previously shown that a checkpoint dependent on MEC1 and RAD53 slows the rate of S phase progression in Saccharomyces cerevisiae in response to alkylation damage. Whereas wild-type cells exhibit a slow S phase in response to damage, mec1-1 and rad53 mutants replicate rapidly in the presence or absence of DNA damage. In this report, we show that other genes ( RAD9, RAD17, RAD24 ) involved in the DNA damage checkpoint pathway also play a role in regulating S phase in response to DNA damage. Furthermore, RAD9, RAD17, and RAD24 fall into two groups with respect to both sensitivity to alkylation and regulation of S phase. We also demonstrate that the more dramatic defect in S phase regulation in the mec1-1 and rad53 mutants is epistatic to a less severe defect seen in rad9 Δ, rad17 Δ, and rad24 Δ. Furthermore, the triple rad9 Δ rad17 Δ rad24 Δ mutant also has a less severe defect than mec1-1 or rad53 mutants. Finally, we demonstrate the specificity of this phenotype by showing that the DNA repair and/or checkpoint mutants mgt1 Δ, mag1 Δ, apn1 Δ, rev3 Δ, rad18 Δ, rad16 Δ, dun1 -Δ 100 , sad4-1 , tel1 Δ, rad26 Δ, rad51 Δ, rad52-1 , rad54 Δ, rad14 Δ, rad1 Δ, pol30–46, pol30–52, mad3 Δ, pds1 Δ/ esp2 Δ, pms1 Δ, mlh1 Δ, and msh2 Δ are all proficient at S phase regulation, even though some of these mutations confer sensitivity to alkylation.

[学科分类] 医学（综合）