在减数分裂同源 DNA 配对中 Hop2-Mnd1 作用的机制见解。
Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing.
机构信息
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.
出版信息
Nucleic Acids Res. 2014 Jan;42(2):906-17. doi: 10.1093/nar/gkt924. Epub 2013 Oct 22.
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.
Hop2-Mnd1 复合物与 DMC1 重组酶在减数分裂重组中协同作用。Hop2-Mnd1 稳定 DMC1-单链 DNA（ssDNA）丝，并促进重组酶丝捕获双链 DNA 伴侣以组装联会复合物。在此，我们定义了 Hop2-Mnd1 在 DMC1 介导的重组中的作用机制。小角度 X 射线散射分析和电子显微镜显示，异二聚体 Hop2-Mnd1 是一个 V 形分子。我们表明该蛋白复合物具有三个不同的 DNA 结合位点，并确定了它们的功能相关性。具体而言，Hop2 和 Mnd1 的 N 端双链 DNA 结合功能协同介导联会复合物的组装，而 Hop2 C 端的 ssDNA 结合有助于稳定 DMC1-ssDNA 丝。提出了一个 Hop2-Mnd1-DMC1-ssDNA 整体模型，以解释它如何介导减数分裂重组中的同源 DNA 配对。
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