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

Zhao, W.; Saro, D.; Hammel, M.; Kwon, Y.; Xu, Y.; Rambo, R. P.; Williams, G. J.; Chi, P.; Lu, L.; Pezza, R. J.; Camerini-Otero, R. D.; Tainer, J. A.; Wang, H. -W.; Sung, P.

doi:10.1093/nar/gkt924

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

Journal Article · Mon Oct 21 00:00:00 EDT 2013 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkt924· OSTI ID:1625532

Zhao, W. ^[1]; Saro, D. ^[2]; Hammel, M. ^[3]; Kwon, Y. ^[2]; Xu, Y. ^[2]; Rambo, R. P. ^[3]; Williams, G. J. ^[3]; Chi, P. ^[4]; Lu, L. ^[2]; Pezza, R. J. ^[5]; Camerini-Otero, R. D. ^[6]; Tainer, J. A. ^[3]; Wang, H. -W. ^[2]; Sung, P. ^[2]

Yale Univ., New Haven, CT (United States); DOE/OSTI
Yale Univ., New Haven, CT (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
National Taiwan Univ., Taipei (Taiwan)
Oklahoma Medical Research Foundation, Oklahoma City, OK (United States)
National Institutes of Health (NIH), Bethesda, MD (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625532

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 2 Vol. 42; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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