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.
authors.affiliation: 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.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhao
authors.forename: Dorina
authors.initials: D
authors.lastname: Saro
authors.forename: Michal
authors.initials: M
authors.lastname: Hammel
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kwon
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Robert P
authors.initials: RP
authors.lastname: Rambo
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Williams
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
authors.forename: Lucy
authors.initials: L
authors.lastname: Lu
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D017354:Point Mutation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D045522:Recombinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501202:Hop2 protein, mouse; C501203:Mnd1 protein, mouse; D045522:Recombinases; D004247:DNA