Interdependence of the Rad50 hook and globular domain functions Journal Article
| Authors: | Hohl, M.; Kochańczyk, T.; Tous, C.; Aguilera, A.; KrEzel, A.; Petrini, J. H. J. |
| Article Title: | Interdependence of the Rad50 hook and globular domain functions |
| Abstract: | Rad50 contains a conserved Zn2+ coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn2+-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. © 2015 Elsevier Inc. |
| Keywords: | controlled study; gene mutation; human cell; nonhuman; protein domain; cohesin; animal cell; mouse; phenotype; mre11 protein; rad50 protein; allele; homologous recombination; sister chromatid; protein protein interaction; gene function; wild type; double stranded dna; fluorescence resonance energy transfer; dna flanking region; dimerization; conformational transition; yeast; protein secondary structure; gene insertion; zinc; mutagenesis; circular dichroism; ultraviolet spectroscopy; dna end joining repair; telomere homeostasis; human; article; globular protein; hook domain |
| Journal Title: | Molecular Cell |
| Volume: | 57 |
| Issue: | 3 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2015-02-05 |
| Start Page: | 479 |
| End Page: | 492 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2014.12.018 |
| PROVIDER: | scopus |
| PUBMED: | 25601756 |
| PMCID: | PMC4527088 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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