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

doi:10.1093/nar/gkt924

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 journal › Article › peer-review

42 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 language	English (US)
Pages (from-to)	906-917
Number of pages	12
Journal	Nucleic acids research
Volume	42
Issue number	2
DOIs	https://doi.org/10.1093/nar/gkt924
State	Published - Jan 1 2014
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1093/nar/gkt924

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@article{0fe0f38b4e5a404fbe0bbe9cc5c642ab,

title = "Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing",

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.",

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

note = "Funding Information: US National Institutes of Health [RO1ES015252, RO1CA168635, RO1ES007061 and PO1CA092584]; the National Science Council of Taiwan [NSC 99-2311-B-002-012 and NSC 100-2311-B-002-009]; and also by the National Basic Research Program of China [2010CB912401] and the National Center for Protein Sciences Beijing. Funding for open access charge: [RO1ES015252,RO1CA168635, RO1ES007061 and PO1CA092584].",

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doi = "10.1093/nar/gkt924",

language = "English (US)",

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T1 - Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing

AU - Zhao, Weixing

AU - Saro, Dorina

AU - Hammel, Michal

AU - Kwon, Youngho

AU - Xu, Yuanyuan

AU - Rambo, Robert P.

AU - Williams, Gareth J.

AU - Chi, Peter

AU - Lu, Lucy

AU - Pezza, Roberto J.

AU - Camerini-Otero, R. Daniel

AU - Tainer, John A.

AU - Wang, Hong Wei

AU - Sung, Patrick

N1 - Funding Information: US National Institutes of Health [RO1ES015252, RO1CA168635, RO1ES007061 and PO1CA092584]; the National Science Council of Taiwan [NSC 99-2311-B-002-012 and NSC 100-2311-B-002-009]; and also by the National Basic Research Program of China [2010CB912401] and the National Center for Protein Sciences Beijing. Funding for open access charge: [RO1ES015252,RO1CA168635, RO1ES007061 and PO1CA092584].

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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JO - Nucleic acids research

JF - Nucleic acids research

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

Abstract

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