The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair

Karl-Peter Hopfner, Lisa Craig, Gabriel Moncalian, Robert A. Zinkel, Takehiko Usui, Barbara A. L. Owen, Annette Karcher, Brendan Henderson, Jean-Luc Bodmer, Cynthia T. McMurray, James P. Carney, John H. J. Petrini () and John A. Tainer ()
Additional contact information
Karl-Peter Hopfner: University of Munich
Lisa Craig: The Scripps Research Institute
Gabriel Moncalian: The Scripps Research Institute
Robert A. Zinkel: University of Wisconsin
Takehiko Usui: Molecular Biology, Memorial Sloan-Kettering Cancer Center
Barbara A. L. Owen: Mayo Clinic and Foundation
Annette Karcher: University of Munich
Brendan Henderson: University of Maryland School of Medicine
Jean-Luc Bodmer: The Scripps Research Institute
Cynthia T. McMurray: Mayo Clinic and Foundation
James P. Carney: University of Maryland School of Medicine
John H. J. Petrini: Molecular Biology, Memorial Sloan-Kettering Cancer Center
John A. Tainer: The Scripps Research Institute

Nature, 2002, vol. 418, issue 6897, 562-566

Abstract: Abstract The Mre11 complex (Mre11–Rad50–Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association1,2,3,4,5,6,7. These functions all imply that the linked binding of two DNA substrates occurs, although the molecular basis for this process remains unknown. Here we present a 2.2 Å crystal structure of the Rad50 coiled-coil region that reveals an unexpected dimer interface at the apex of the coiled coils in which pairs of conserved Cys-X-X-Cys motifs form interlocking hooks that bind one Zn2+ ion. Biochemical, X-ray and electron microscopy data indicate that these hooks can join oppositely protruding Rad50 coiled-coil domains to form a flexible bridge of up to 1,200 Å. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain8. The Rad50 hook is functional, because mutations in this motif confer radiation sensitivity in yeast and disrupt binding at the distant Mre11 nuclease interface. These data support an architectural role for the Rad50 coiled coils in forming metal-mediated bridging complexes between two DNA-binding heads. The resulting assemblies have appropriate lengths and conformational properties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining.

Date: 2002
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DOI: 10.1038/nature00922

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