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

MPG-Autoren
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Toseland,  Christopher P.
Gruber, Stephan / Chromosome Organization and Dynamics, Max Planck Institute of Biochemistry, Max Planck Society;

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Gruber,  Stephan
Gruber, Stephan / Chromosome Organization and Dynamics, Max Planck Institute of Biochemistry, Max Planck Society;

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Nucl. Acids Res.-2015-Kang-3841-56.pdf
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Kang, H.-A., Shin, H.-C., Kalantzi, A.-S., Toseland, C. P., Kim, H.-M., Gruber, S., et al. (2015). Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination. NUCLEIC ACIDS RESEARCH, 43(7), 3841-3856. doi:10.1093/nar/gkv172.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0027-A85C-D
Zusammenfassung
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 alpha-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.