Institut Jean-Pierre Bourgin, UMR1318 INRA-AgroParisTech, Université Paris-Saclay, RD10,Versailles, France.
Université Paris-Sud, Université Paris-Saclay, Orsay, France.
PLoS Genet. 2018 Apr 2;14(4):e1007317. doi: 10.1371/journal.pgen.1007317. eCollection 2018 Apr.
Homologous recombination is central to repair DNA double-strand breaks, either accidently arising in mitotic cells or in a programed manner at meiosis. Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny. However, mechanisms regulating crossover formation remain elusive. Here, we identified through genetic and protein-protein interaction screens FIDGETIN-LIKE-1 INTERACTING PROTEIN (FLIP) as a new partner of the previously characterized anti-crossover factor FIDGETIN-LIKE-1 (FIGL1) in Arabidopsis thaliana. We showed that FLIP limits meiotic crossover together with FIGL1. Further, FLIP and FIGL1 form a protein complex conserved from Arabidopsis to human. FIGL1 interacts with the recombinases RAD51 and DMC1, the enzymes that catalyze the DNA strand exchange step of homologous recombination. Arabidopsis flip mutants recapitulate the figl1 phenotype, with enhanced meiotic recombination associated with change in counts of DMC1 and RAD51 foci. Our data thus suggests that FLIP and FIGL1 form a conserved complex that regulates the crucial step of strand invasion in homologous recombination.
同源重组是修复 DNA 双链断裂的核心机制，这种断裂要么在有丝分裂细胞中偶然产生，要么在减数分裂中以程序化的方式产生。减数分裂断裂修复产生的交叉对于正确的染色体分离和增加后代的遗传多样性至关重要。然而，调节交叉形成的机制仍然难以捉摸。在这里，我们通过遗传和蛋白质-蛋白质相互作用筛选鉴定了 FIDGETIN-LIKE-1 INTERACTING PROTEIN（FLIP），它是拟南芥中先前表征的抗交叉因子 FIDGETIN-LIKE-1（FIGL1）的新伴侣。我们表明，FLIP 与 FIGL1 一起限制减数分裂交叉。此外，FLIP 和 FIGL1 形成一个从拟南芥到人类保守的蛋白质复合物。FIGL1 与重组酶 RAD51 和 DMC1 相互作用，RAD51 和 DMC1 是催化同源重组 DNA 链交换步骤的酶。拟南芥 flip 突变体重现了 figl1 表型，与 DMC1 和 RAD51 焦点计数变化相关的减数分裂重组增强。因此，我们的数据表明，FLIP 和 FIGL1 形成了一个保守的复合物，调节同源重组中链入侵的关键步骤。
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