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

Nucleic Acids Research
Hyun-Ah KangByung-Ha Oh

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 α-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.

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Citations

May 23, 2017·Journal of Biomolecular Structure & Dynamics·Hem Moktan, Donghua H Zhou
Jul 27, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Wataru KobayashiHitoshi Kurumizaka
Oct 24, 2017·Asian-Australasian Journal of Animal Sciences·Yixin WangMingzhou Li
Jun 21, 2018·Annual Review of Microbiology·Gareth Bloomfield
Nov 30, 2018·Cell Cycle·J Brooks Crickard, Eric C Greene
May 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Hideo TsubouchiHiroshi Iwasaki
Jan 5, 2019·Chromosoma·Orla M Dunne, Owen R Davies
Oct 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·Chih-Hao LuHung-Wen Li
Jun 27, 2018·Nature Protocols·Zsuzsanna Orbán-NémethKarl Mechtler
Feb 1, 2020·Pharmacology & Therapeutics·Erik LauriniSabrina Pricl
Sep 10, 2018·DNA Repair·J Brooks Crickard, Eric C Greene

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Methods Mentioned

BETA
X-ray
electrophoresis
proteolysis

Software Mentioned

CNS
SOLVE
UCSF Chimera
Dali
COOT
NAMD
HHpred
BLAST
3DNA
LeaP

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