Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.
Department of Genetics and Development, Columbia University, New York, NY, USA.
EMBO J. 2018 Apr 3;37(7). doi: 10.15252/embj.201798728. Epub 2018 Feb 14.
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.
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。