Functions of Saccharomyces cerevisiae 14-3-3 proteins in response to DNA damage and to DNA replication stress.

摘要: Two members of the 14-3-3 protein family, involved in key biological processes different eukaryotes, are encoded by functionally redundant Saccharomyces cerevisiae BMH1 and BMH2 genes. We produced characterized 12 independent bmh1 mutant alleles, whose presence cell as sole source causes hypersensitivity to genotoxic agents, indicating that Bmh proteins required for proper response DNA damage. In particular, bmh1-103 bmh1-266 alleles cause defects G1/S G2/M damage checkpoints, whereas only checkpoint is altered bmh1-169 bmh1-221 alleles. Impaired responses correlate with inability maintain phosphorylated forms Rad53 and/or Chk1, suggesting might regulate phosphorylation/dephosphorylation these kinases. Moreover, several bmh2Delta mutants defective resuming replication after transient deoxynucleotide depletion, all display synthetic effects when also carrying mutations affecting polalpha-primase RPA complexes, a role stress response. Finally, bmh1-170 show increased rates spontaneous gross chromosomal rearrangements, suppress genome instability.