Kobayashi Wataru, Hosoya Noriko, Machida Shinichi, Miyagawa Kiyoshi, Kurumizaka Hitoshi
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
Genes Cells. 2017 Sep;22(9):799-809. doi: 10.1111/gtc.12513. Epub 2017 Jul 26.
The synaptonemal complex is a higher-ordered proteinaceous architecture formed between homologous chromosomes. SYCP3 is a major component of the lateral/axial elements in the synaptonemal complex and is essential for meiotic recombination. Previous genetic studies showed that SYCP3 functions in meiotic homologous recombination biased to interhomologous chromosomes, by regulating the strand invasion activities of the RAD51 and DMC1 recombinases. However, the mechanism by which SYCP3 regulates RAD51- and DMC1-mediated strand invasion remains elusive. In this study, we found that SYCP3 significantly suppresses the RAD51-mediated, but not the DMC1-mediated, strand invasion reaction by competing with HOP2-MND1, which is an activator for both RAD51 and DMC1. A SYCP3 mutant with defective RAD51 binding does not inhibit the RAD51-mediated homologous recombination in human cells. Therefore, SYCP3 may promote the DMC1-driven homologous recombination by attenuating the RAD51 activity during meiosis.
联会复合体是在同源染色体之间形成的一种高级蛋白质结构。SYCP3是联会复合体中侧/轴元件的主要成分，对减数分裂重组至关重要。先前的遗传学研究表明，SYCP3通过调节RAD51和DMC1重组酶的链入侵活性，在偏向同源染色体间的减数分裂同源重组中发挥作用。然而，SYCP3调节RAD51和DMC1介导的链入侵的机制仍不清楚。在本研究中，我们发现SYCP3通过与HOP2-MND1竞争，显著抑制RAD51介导的而非DMC1介导的链入侵反应，HOP2-MND1是RAD51和DMC1的激活剂。具有缺陷的RAD51结合能力的SYCP3突变体不会抑制人类细胞中RAD51介导的同源重组。因此，SYCP3可能通过在减数分裂过程中减弱RAD51活性来促进DMC1驱动的同源重组。
