The Saccharomyces Cerevisiae 14-3-3 Proteins Bmh1 and Bmh2 Directly Influence the Dna Damage-dependent Functions of Rad53.
From: Laboratory of Chromosome Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Feb 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 8
- Pages: 2797-802
- Medium: Print
- Language: English
- Citation (JAMA): Usui Takehiko, Petrini John H J, et al. The Saccharomyces Cerevisiae 14-3-3 Proteins Bmh1 and Bmh2 Directly Influence the Dna Damage-dependent Functions of Rad53.. Proc. Natl. Acad. Sci. U.S.A. Feb 2007;104:2797-802
Abstract
In this study, we mutated autophosphorylation sites in Rad53 based on their conservation with previously identified autophosphorylation sites in the mammalian Rad53 ortholog, Chk2. As with wild-type Rad53, the autophosphorylation mutant, rad53-TA, undergoes Mec1/Tel1-dependent interactions with Rad9 and Dun1 in response to genotoxic stress. Whereas rad53-TA in vitro kinase activity is severely impaired, the rad53-TA strains are not completely deficient for cell-cycle checkpoint functions, indicating that the mutant kinase retains a basal level of function. We describe a genetic interaction among Rad53, Dun1, and the 14-3-3 proteins Bmh1 and Bmh2 and present evidence that 14-3-3 proteins directly facilitate Rad53 function in vivo. The data presented account for the previously observed checkpoint defects associated with 14-3-3 mutants in Saccharomyces pombe and Saccharomyces cerevisiae. The 14-3-3 functional interaction appears to modulate Rad53 activity, reminiscent of 14-3-3’s effect on human Raf1 kinase and distinct from the indirect mode of regulation by 14-3-3 observed for Chk1 or Cdc25.
Mesh Headings (Keywords): 14-3-3 Proteins, Binding Sites, Cell Cycle Proteins, DNA Damage, Gene Dosage, Immunoprecipitation, Mutant Proteins, Phenotype, Phosphopeptides, Protein Binding, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Suppression, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17299042
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