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The Rad50 hook domain is a critical determinant of Mre11 complex functions.
Nat Struct Mol Biol. 2005 May; 12(5):403-7.NS

Abstract

The Mre11 complex (in Saccharomyces cerevisiae: Mre11, Rad50 and Xrs2) influences multiple facets of chromosome break metabolism. A conserved feature of the Mre11 complex is a zinc-coordinating motif in Rad50 called the Rad50 hook. We established a diploid yeast strain, rad50(hook), in which Rad50 is encoded in halves, one from each of the two RAD50 alleles, with the residues constituting the hook deleted. In all respects, rad50(hook) phenocopies complete Rad50 deficiency. Replacing the hook domain with a ligand-inducible FKBP dimerization cassette partially mitigated all phenotypes in a ligand-dependent manner. The data indicate that the Rad50 hook is critical for Mre11 complex-dependent DNA repair, telomere maintenance and meiotic double-strand break formation. Sister chromatid cohesion was unaffected by Rad50 deficiency, suggesting that molecular bridging required for recombinational DNA repair is qualitatively distinct from cohesin-mediated sister chromatid cohesion.

Authors+Show Affiliations

Molecular Biology Program, Memorial Sloan Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, RRL 901B, 1275 York Avenue, New York, New York 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15852023

Citation

Wiltzius, Jed J W., et al. "The Rad50 Hook Domain Is a Critical Determinant of Mre11 Complex Functions." Nature Structural & Molecular Biology, vol. 12, no. 5, 2005, pp. 403-7.
Wiltzius JJ, Hohl M, Fleming JC, et al. The Rad50 hook domain is a critical determinant of Mre11 complex functions. Nat Struct Mol Biol. 2005;12(5):403-7.
Wiltzius, J. J., Hohl, M., Fleming, J. C., & Petrini, J. H. (2005). The Rad50 hook domain is a critical determinant of Mre11 complex functions. Nature Structural & Molecular Biology, 12(5), 403-7.
Wiltzius JJ, et al. The Rad50 Hook Domain Is a Critical Determinant of Mre11 Complex Functions. Nat Struct Mol Biol. 2005;12(5):403-7. PubMed PMID: 15852023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Rad50 hook domain is a critical determinant of Mre11 complex functions. AU - Wiltzius,Jed J W, AU - Hohl,Marcel, AU - Fleming,James C, AU - Petrini,John H J, Y1 - 2005/04/24/ PY - 2005/03/10/received PY - 2005/03/23/accepted PY - 2005/4/27/pubmed PY - 2005/6/23/medline PY - 2005/4/27/entrez SP - 403 EP - 7 JF - Nature structural & molecular biology JO - Nat Struct Mol Biol VL - 12 IS - 5 N2 - The Mre11 complex (in Saccharomyces cerevisiae: Mre11, Rad50 and Xrs2) influences multiple facets of chromosome break metabolism. A conserved feature of the Mre11 complex is a zinc-coordinating motif in Rad50 called the Rad50 hook. We established a diploid yeast strain, rad50(hook), in which Rad50 is encoded in halves, one from each of the two RAD50 alleles, with the residues constituting the hook deleted. In all respects, rad50(hook) phenocopies complete Rad50 deficiency. Replacing the hook domain with a ligand-inducible FKBP dimerization cassette partially mitigated all phenotypes in a ligand-dependent manner. The data indicate that the Rad50 hook is critical for Mre11 complex-dependent DNA repair, telomere maintenance and meiotic double-strand break formation. Sister chromatid cohesion was unaffected by Rad50 deficiency, suggesting that molecular bridging required for recombinational DNA repair is qualitatively distinct from cohesin-mediated sister chromatid cohesion. SN - 1545-9993 UR - https://www.unboundmedicine.com/medline/citation/15852023/The_Rad50_hook_domain_is_a_critical_determinant_of_Mre11_complex_functions_ L2 - https://doi.org/10.1038/nsmb928 DB - PRIME DP - Unbound Medicine ER -