RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage.
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, rad 17 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.
Paulovich
A G
AG
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Margulies
R U
RU
Garvik
B M
BM
Hartwell
L H
LH
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics*; D016193:G1 Phase; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005804:Genes, Lethal; D016153:Genes, Suppressor; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics*
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; C088385:RAD24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae