Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan;
Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa 226-8503, Japan.
Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12062-12070. doi: 10.1073/pnas.1917419117. Epub 2020 May 15.
Homologous recombination (HR) is a universal mechanism operating in somatic and germ-line cells, where it contributes to the maintenance of genome stability and ensures the faithful distribution of genetic material, respectively. The ability to identify and exchange the strands of two homologous DNA molecules lies at the heart of HR and is mediated by RecA-family recombinases. Dmc1 is a meiosis-specific RecA homolog in eukaryotes, playing a predominant role in meiotic HR. However, Dmc1 cannot function without its two major auxiliary factor complexes, Swi5-Sfr1 and Hop2-Mnd1. Through biochemical reconstitutions, we demonstrate that Swi5-Sfr1 and Hop2-Mnd1 make unique contributions to stimulate Dmc1-driven strand exchange in a synergistic manner. Mechanistically, Swi5-Sfr1 promotes establishment of the Dmc1 nucleoprotein filament, whereas Hop2-Mnd1 defines a critical, rate-limiting step in initiating strand exchange. Following execution of this function, we propose that Swi5-Sfr1 then promotes strand exchange with Hop2-Mnd1. Thus, our findings elucidate distinct yet complementary roles of two auxiliary factors in Dmc1-driven strand exchange, providing mechanistic insights into some of the most critical steps in meiotic HR.
同源重组（HR）是一种在体细胞和生殖细胞中普遍存在的机制，它分别有助于维持基因组稳定性和确保遗传物质的忠实分配。识别和交换两条同源 DNA 分子链的能力是 HR 的核心，由 RecA 家族重组酶介导。Dmc1 是真核生物减数分裂特异性的 RecA 同源物，在减数分裂 HR 中起着主要作用。然而，Dmc1 的功能离不开其两个主要的辅助因子复合物，Swi5-Sfr1 和 Hop2-Mnd1。通过生化重建，我们证明 Swi5-Sfr1 和 Hop2-Mnd1 以协同方式对 Dmc1 驱动的链交换产生独特的促进作用。从机制上讲，Swi5-Sfr1 促进 Dmc1 核蛋白丝的建立，而 Hop2-Mnd1 确定起始链交换的关键限速步骤。执行此功能后，我们提出 Swi5-Sfr1 随后与 Hop2-Mnd1 促进链交换。因此，我们的发现阐明了两个辅助因子在 Dmc1 驱动的链交换中的不同但互补的作用，为减数分裂 HR 中的一些最关键步骤提供了机制上的见解。
