Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing

作者:Zhao, Weixing; Saro, Dorina; Hammel, Michal; Kwon, YoungHo; Xu, Yuanyuan; Rambo, Robert P.; Williams, Gareth J.; Chi, Peter; Lu, Lucy; Pezza, Roberto J.; Camerini-Otero, R. Daniel; Tainer, John A.; Wang, Hong-Wei; Sung, Patrick*
来源:Nucleic Acids Research, 2014, 42(2): 906-917.
DOI:10.1093/nar/gkt924

摘要

The Hop2-Mnd1 complex functions with the DMC1 recombinase in meiotic recombination. Hop2-Mnd1 stabilizes the DMC1-single-stranded DNA (ssDNA) filament and promotes the capture of the double-stranded DNA partner by the recombinase filament to assemble the synaptic complex. Herein, we define the action mechanism of Hop2-Mnd1 in DMC1-mediated recombination. Small angle X-ray scattering analysis and electron microscopy reveal that the heterodimeric Hop2-Mnd1 is a V-shaped molecule. We show that the protein complex harbors three distinct DNA binding sites, and determine their functional relevance. Specifically, the N-terminal double-stranded DNA binding functions of Hop2 and Mnd1 co-operate to mediate synaptic complex assembly, whereas ssDNA binding by the Hop2 C-terminus helps stabilize the DMC1-ssDNA filament. A model of the Hop2-Mnd1-DMC1-ssDNA ensemble is proposed to explain how it mediates homologous DNA pairing in meiotic recombination.