Maintenance of the DNA-Damage Checkpoint Requires DNA-Damage-Induced Mediator Protein Oligomerization Journal Article
| Authors: | Usui, T.; Foster, S. S.; Petrini, J. H. J. |
| Article Title: | Maintenance of the DNA-Damage Checkpoint Requires DNA-Damage-Induced Mediator Protein Oligomerization |
| Abstract: | Oligomeric assembly of Brca1 C-terminal (BRCT) domain-containing mediator proteins occurs at sites of DNA damage. However, the functional significance and regulation of such assemblies are not well understood. In this study, we defined the molecular mechanism of DNA-damage-induced oligomerization of the S. cerevisiae BRCT protein Rad9. Our data suggest that Rad9's tandem BRCT domain mediates Rad9 oligomerization via its interaction with its own Mec1/Tel1-phosphorylated SQ/TQ cluster domain (SCD). Rad53 activation is unaffected by mutations that impair Rad9 oligomerization, but checkpoint maintenance is lost, indicating that oligomerization is required to sustain checkpoint signaling. Once activated, Rad53 phosphorylates the Rad9 BRCT domain, which attenuates the BRCT-SCD interaction. Failure to phosphorylate the Rad9 BRCT results in cytologically visible Rad9 foci. This suggests a feedback loop wherein Rad53 activity and Rad9 oligomerization are regulated to tune the DNA-damage response. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; protein phosphorylation; mutation; protein domain; cytology; cell cycle proteins; dna damage; signaling; protein protein interaction; phosphorylation; brca1 protein; dna; protein-serine-threonine kinases; intracellular signaling peptides and proteins; checkpoint kinase 2; protein structure, tertiary; binding sites; saccharomyces cerevisiae proteins; oligomerization; genes, cdc; protein rad9; dna, fungal |
| Journal Title: | Molecular Cell |
| Volume: | 33 |
| Issue: | 2 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2009-01-30 |
| Start Page: | 147 |
| End Page: | 159 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2008.12.022 |
| PUBMED: | 19187758 |
| PROVIDER: | scopus |
| PMCID: | PMC2995296 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: MOCEF" - "Source: Scopus" |
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