Genetics, Vol 145, 45-62, Copyright © 1997

INVESTIGATIONS

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

A. G. Paulovich, R. U. Margulies, B. M. Garvik and L. H. Hartwell
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104

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{Delta}, rad17{Delta}, and rad24{Delta}. Furthermore, the triple rad9{Delta} rad17{Delta} rad24{Delta} 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{Delta}, mag1{Delta}, apn1{Delta}, rev3{Delta}, rad18{Delta}, rad16{Delta}, dun1-{Delta}100, sad4-1, tel1{Delta}, rad26{Delta}, rad51{Delta}, rad52-1, rad54{Delta}, rad14{Delta}, rad1{Delta}, pol30-46, pol30-52, mad3{Delta}, pds1{Delta}/esp2{Delta}, pms1{Delta}, mlh1{Delta}, and msh2{Delta} are all proficient at S phase regulation, even though some of these mutations confer sensitivity to alkylation.


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