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Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

Kang, Hyun-Ah, Shin, Ho-Chul, Kalantzi, Alexandra-Styliani, Toseland, Christopher P., Kim, Hyun-Min, Gruber, Stephan, Dal Peraro, Matteo, Oh, Byung-Ha (2015) Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination. Nucleic acids research, 43 (7). pp. 1-12. ISSN 1362-4962. (doi:10.1093/nar/gkv172) (KAR id:47843)

Abstract

In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2-Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra ?-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion.

Item Type: Article
DOI/Identification number: 10.1093/nar/gkv172
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Chris Toseland
Date Deposited: 07 Apr 2015 12:02 UTC
Last Modified: 07 Feb 2020 14:25 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/47843 (The current URI for this page, for reference purposes)

University of Kent Author Information

Toseland, Christopher P..

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