TY - JOUR
T1 - The Rad50 coiled-coil domain is indispensable for Mre11 complex functions
AU - Hohl, Marcel
AU - Kwon, Youngho
AU - Galván, Sandra Muñoz
AU - Xue, Xiaoyu
AU - Tous, Cristina
AU - Aguilera, Andrés
AU - Sung, Patrick
AU - Petrini, John H.J.
N1 - Funding Information:
We are grateful to J. Haber (Brandeis University), F. Uhlmann (London Research Institute), L. Symington (Columbia University), S. Keeney (Memorial Sloan-Kettering Cancer Center), A. Amon (Massachusetts Institute of Technology) and T. Wilson (University of Michigan) for yeast strains, reagents and technical support, to K.-P. Hopfner for structural advice, to G. Bryant and D. Spagna for help with the qPCR, and to current and former members of the Petrini laboratory for insightful comments. We thank S. Keeney for critical reading of the manuscript. This work was supported by GM56888 (J.H.J.P.), PBZH33-112756 and PA0033-117484 from the Swiss National Science Foundation and the Eugen and Elisabeth Schellenberg Foundation (M.H.), BFU2006-05260 and Consolider Ingenio 2010 CSD2007-015 from the Spanish Ministry of Science and Innovation (A.A.) and ES07061 (P.S.).
PY - 2010/10
Y1 - 2010/10
N2 - The Mre11 complex (Mre11, Rad50 and Xrs2 in Saccharomyces cerevisiae) influences diverse functions in the DNA damage response. The complex comprises the globular DNA-binding domain and the Rad50 hook domain, which are linked by a long and extended Rad50 coiled-coil domain. In this study, we constructed rad50 alleles encoding truncations of the coiled-coil domain to determine which Mre11 complex functions required the full length of the coils. These mutations abolished telomere maintenance and meiotic double-strand break (DSB) formation, and severely impaired homologous recombination, indicating a requirement for long-range action. Nonhomologous end joining, which is probably mediated by the globular domain of the Mre11 complex, was also severely impaired by alteration of the coiled-coil and hook domains, providing the first evidence of their influence on this process. These data show that functions of Mre11 complex are integrated by the coiled coils of Rad50.
AB - The Mre11 complex (Mre11, Rad50 and Xrs2 in Saccharomyces cerevisiae) influences diverse functions in the DNA damage response. The complex comprises the globular DNA-binding domain and the Rad50 hook domain, which are linked by a long and extended Rad50 coiled-coil domain. In this study, we constructed rad50 alleles encoding truncations of the coiled-coil domain to determine which Mre11 complex functions required the full length of the coils. These mutations abolished telomere maintenance and meiotic double-strand break (DSB) formation, and severely impaired homologous recombination, indicating a requirement for long-range action. Nonhomologous end joining, which is probably mediated by the globular domain of the Mre11 complex, was also severely impaired by alteration of the coiled-coil and hook domains, providing the first evidence of their influence on this process. These data show that functions of Mre11 complex are integrated by the coiled coils of Rad50.
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U2 - 10.1038/nsmb.2116
DO - 10.1038/nsmb.2116
M3 - Article
C2 - 21892167
AN - SCOPUS:80455173885
SN - 1545-9993
VL - 18
SP - 1124
EP - 1131
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -