SYCP3 regulates strand invasion activities of RAD51 and DMC1
SYCP3 regulates strand invasion activities of RAD51 and DMC1
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DOI：
10.1111/gtc.12513
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发表时间：
2017-09-01
期刊：
影响因子：
2.1
通讯作者：
Kurumizaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Wataru;Hosoya, Noriko;Kurumizaka, Hitoshi
联会复合体是在同源染色体之间形成的一种更高级的蛋白质结构。SYCP3是联会复合体中侧向/轴向成分的主要组成部分，是减数分裂重组所必需的。以往的遗传学研究表明，SYCP3通过调节RAD51和DMC1重组酶的链侵袭活性，在减数分裂同源重组中发挥偏向同源染色体的作用。然而，SYCP3调节RAD51和DMC1介导的链侵袭的机制仍然不清楚。在本研究中，我们发现SYCP3通过与同时激活RAD51和DMC1的HOP2-MND1竞争，显著抑制RAD51介导的链侵袭反应，而不是DMC1介导的链侵袭反应。具有RAD51结合缺陷的SYCP3突变体不抑制RAD51介导的人类细胞中的同源重组。因此，SYCP3可能通过减弱减数分裂过程中RAD51的活性来促进DMC1驱动的同源重组。
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.