Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex

Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex
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DOI:
10.1074/jbc.m506506200
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发表时间:
2006-03-03
影响因子:
4.8
通讯作者:
Yokoyama, S
Yokoyama, S
中科院分区:
生物学2区
文献类型:
--
作者:
Enomoto, R;Kinebuchi, T;Yokoyama, S

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在酿酒酵母(Saccharomyces cerevisiae)中,Hop2蛋白与Mnd1蛋白形成复合体,在减数分裂期间同源染色体的排列需要Hop2蛋白,这可能是通过它们之间广泛的同源性匹配实现的。真核生物RecA同源物Rad51和Dmc1蛋白促进链交换,并可能在配对DNA分子内广泛的同源性匹配中起作用。在本研究中,我们纯化了人TBPIP/ Hop2-Mnd1复合物,发现它能显著刺激Dmc1-和rad51介导的链交换。人类Hop2-Mnd1复合体优先结合三链DNA分支,模拟链交换中间体。这些发现与遗传数据一致,表明同源染色体之间的同源性匹配需要Hop2和Mnd1蛋白。因此,人类TBPIP/ Hop2-Mnd1复合体可能通过刺激减数分裂过程中的链交换来确保同源染色体之间的正确配对。
In Saccharomyces cerevisiae, the Hop2 protein forms a complex with the Mnd1 protein and is required for the alignment of homologous chromosomes during meiosis, probably through extensive homology matching between them. The Rad51 and Dmc1 proteins, the eukaryotic RecA orthologs, promote strand exchange and may function in the extensive matching of homology within paired DNA molecules. In the present study, we purified the human TBPIP/ Hop2-Mnd1 complex and found that it significantly stimulates the Dmc1- and Rad51-mediated strand exchange. The human Hop2-Mnd1 complex preferentially binds to a three-stranded DNA branch, which mimics the strand-exchange intermediate. These findings are consistent with genetic data, which showed that the Hop2 and Mnd1 proteins are required for homology matching between homologous chromosomes. Therefore, the human TBPIP/ Hop2-Mnd1 complex may ensure proper pairing between homologous chromosomes through its stimulation of strand exchange during meiosis.