Budding yeast 14-3-3 proteins contribute to the robustness of the DNA damage and spindle checkpoints.
Cells respond to DNA or mitotic spindle damage by activating specific pathways that halt the cell cycle to allow for possible repair. Here, we report that inactivation of one of the Saccharomyces cerevisiae 14-3-3 proteins, Bmh1, as well as the bmh1-S189P bmh2 mutant, failed to exhibit normal spindle damage-induced cell cycle delay and conferred hypersensitivity to benomyl or nocodazole. These defects were additive with those conferred by the bub2 and mad2 spindle checkpoint mutations. Following cdc13-1-induced DNA damage, the 14-3-3 response was additive with those provided by the Mec1 (ATR-related)-controlled Rad53 (CHK2-related) and Chk1 (CHK1-related) checkpoint pathways and also distinct from the PKA (Protein Kinase A)-controlled response. Therefore, the budding yeast 14-3-3 proteins contribute to the robustness of the two major mitotic checkpoints and, by doing so, may also ensure optimal coordination between the responses to two distinct types of damage.
Grandin
Nathalie
N
IFR128 BioSciences Gerland, UMR CNRS/ENS n degrees 5239, Ecole Normale Supérieure de Lyon, Lyon, France.
Charbonneau
Michel
M
D048948:14-3-3 Proteins / Q000378:metabolism*; D019943:Amino Acid Substitution / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000378:metabolism; D004249:DNA Damage; D009154:Mutation / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects; D034501:Telomere-Binding Proteins / Q000378:metabolism
D048948:14-3-3 Proteins; C075852:BMH1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D015739:Nocodazole