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

Weixing Zhao, Dorina Saro, Michal Hammel, Youngho Kwon, Yuanyuan Xu, Robert P. Rambo, Gareth J. Williams, Peter Chi, Lucy Lu, Roberto J. Pezza, R. Daniel Camerini-Otero, John A. Tainer, Hong Wei Wang, Patrick Sung

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)906-917
Number of pages12
JournalNucleic acids research
Volume42
Issue number2
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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