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Nucleic Acids Res. 2014 Jan;42(2):906-17. doi: 10.1093/nar/gkt924. Epub 2013 Oct 22.

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

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, Cell Cycle and Cancer Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA, Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA and Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

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.

PMID:
24150939
PMCID:
PMC3902922
DOI:
10.1093/nar/gkt924
[Indexed for MEDLINE]
Free PMC Article
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