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调控 Hed1 和 Rad54 结合在减数分裂特异性突触前复合物成熟过程中的作用。

Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific presynaptic complex.

机构信息

Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.

Department of Genetics and Development, Columbia University, New York, NY, USA.

出版信息

EMBO J. 2018 Apr 3;37(7). doi: 10.15252/embj.201798728. Epub 2018 Feb 14.

Abstract

Most eukaryotes have two Rad51/RecA family recombinases, Rad51, which promotes recombination during mitotic double-strand break (DSB) repair, and the meiosis-specific recombinase Dmc1. During meiosis, the strand exchange activity of Rad51 is downregulated through interactions with the meiosis-specific protein Hed1, which helps ensure that strand exchange is driven by Dmc1 instead of Rad51. Hed1 acts by preventing Rad51 from interacting with Rad54, a cofactor required for promoting strand exchange during homologous recombination. However, we have a poor quantitative understanding of the regulatory interplay between these proteins. Here, we use real-time single-molecule imaging to probe how the Hed1- and Rad54-mediated regulatory network contributes to the identity of mitotic and meiotic presynaptic complexes. Based on our findings, we define a model in which kinetic competition between Hed1 and Rad54 helps define the functional identity of the presynaptic complex as cells undergo the transition from mitotic to meiotic repair.

摘要

大多数真核生物有两种 Rad51/RecA 家族重组酶,Rad51,它促进有丝分裂双链断裂 (DSB) 修复过程中的重组,以及减数分裂特异性重组酶 Dmc1。在减数分裂过程中,Rad51 的链交换活性通过与减数分裂特异性蛋白 Hed1 的相互作用而被下调,这有助于确保链交换由 Dmc1 而不是 Rad51 驱动。Hed1 通过防止 Rad51 与 Rad54 相互作用来发挥作用,Rad54 是同源重组过程中促进链交换所必需的辅助因子。然而,我们对这些蛋白质之间的调控相互作用的定量理解还很欠缺。在这里,我们使用实时单分子成像技术来探究 Hed1 和 Rad54 介导的调控网络如何有助于有丝分裂和减数分裂前导复合物的身份。根据我们的发现,我们定义了一个模型,其中 Hed1 和 Rad54 之间的动力学竞争有助于定义前导复合物的功能身份,因为细胞从有丝分裂向减数分裂修复转变。

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