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The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair.
Nature. 2002 Aug 01; 418(6897):562-6.Nat

Abstract

The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. 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 A 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 Zn(2+) 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 A. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain. 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.

Authors+Show Affiliations

[1] Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Gene Center and Institute of Biochemistry, University of Munich, 81377 Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12152085

Citation

Hopfner, Karl-Peter, et al. "The Rad50 Zinc-hook Is a Structure Joining Mre11 Complexes in DNA Recombination and Repair." Nature, vol. 418, no. 6897, 2002, pp. 562-6.
Hopfner KP, Craig L, Moncalian G, et al. The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature. 2002;418(6897):562-6.
Hopfner, K. P., Craig, L., Moncalian, G., Zinkel, R. A., Usui, T., Owen, B. A., Karcher, A., Henderson, B., Bodmer, J. L., McMurray, C. T., Carney, J. P., Petrini, J. H., & Tainer, J. A. (2002). The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature, 418(6897), 562-6.
Hopfner KP, et al. The Rad50 Zinc-hook Is a Structure Joining Mre11 Complexes in DNA Recombination and Repair. Nature. 2002 Aug 1;418(6897):562-6. PubMed PMID: 12152085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. AU - Hopfner,Karl-Peter, AU - Craig,Lisa, AU - Moncalian,Gabriel, AU - Zinkel,Robert A, AU - Usui,Takehiko, AU - Owen,Barbara A L, AU - Karcher,Annette, AU - Henderson,Brendan, AU - Bodmer,Jean-Luc, AU - McMurray,Cynthia T, AU - Carney,James P, AU - Petrini,John H J, AU - Tainer,John A, PY - 2002/8/2/pubmed PY - 2002/8/22/medline PY - 2002/8/2/entrez SP - 562 EP - 6 JF - Nature JO - Nature VL - 418 IS - 6897 N2 - The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. 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 A 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 Zn(2+) 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 A. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain. 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. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/12152085/The_Rad50_zinc_hook_is_a_structure_joining_Mre11_complexes_in_DNA_recombination_and_repair_ L2 - https://doi.org/10.1038/nature00922 DB - PRIME DP - Unbound Medicine ER -