The Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 directly influence the DNA damage-dependent functions of Rad53 Journal Article
| Authors: | Usui, T.; Petrini, J. H. J. |
| Article Title: | The Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 directly influence the DNA damage-dependent functions of Rad53 |
| 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. © 2007 by The National Academy of Sciences of the USA. |
| Keywords: | protein phosphorylation; nonhuman; phenotype; mammalia; cell cycle proteins; dna damage; cell cycle; protein protein interaction; protein binding; enzyme activity; autophosphorylation; dna; saccharomyces cerevisiae; protein-serine-threonine kinases; immunoprecipitation; plasmid; binding site; checkpoint kinase 2; binding sites; yeast; mutant proteins; saccharomyces cerevisiae proteins; gene dosage; enzyme assay; 14-3-3 proteins; ultraviolet irradiation; phosphopeptide; phosphopeptides; kinase; dna damage checkpoint; protein 14 3 3; phosphopeptide binding; suppression, genetic; saccharomyces pombe |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 104 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2007-02-20 |
| Start Page: | 2797 |
| End Page: | 2802 |
| Language: | English |
| DOI: | 10.1073/pnas.0611259104 |
| PUBMED: | 17299042 |
| PROVIDER: | scopus |
| PMCID: | PMC1797148 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
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