Budding yeast DNA damage adaptation mutants exhibit defects in mitotic exit.
In the presence of double strand breaks, DNA damage checkpoint halts cell cycle progression. However, cells ultimately escape the checkpoint arrest and reenter cell cycle in the presence of irreparable DNA damage. cdc5-ad was identified as a mutant that fails to adapt to the cell cycle arrest induced by DNA damage checkpoint. In budding yeast, Cdc5 protein kinase is a component of both MEN and FEAR pathways that are required for mitotic exit. It remains unclear whether the adaptation defect of cdc5-ad mutant cells is related to the function of Cdc5 in mitotic exit. Here we present evidence indicating that cdc5-ad mutant cells exhibit defects in mitotic exit. cdc5-ad mutant cells are sensitive to high dosage of Amn1, a negative regulator of MEN. It also shows synthetic growth defects with mutants in MEN pathway. Moreover, mutants in FEAR pathway exhibit defects in DNA damage adaptation. Thus, we conclude that the compromised mitotic exit pathway contributes to DNA damage adaptation defects in cdc5-ad mutant cells.
Jin
Fengzhi
F
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida 32306, USA.
Wang
Yanchang
Y
D000222:Adaptation, Physiological; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000633:toxicity; D019926:Cyclin B / Q000378:metabolism; D004249:DNA Damage; D015870:Gene Expression; D008938:Mitosis; D009154:Mutation / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000633:toxicity; D004718:Saccharomycetales / Q000166:cytology* / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development
C473476:Amn1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae