The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination

INO80 is an evolutionary conserved nucleosome remodelling complex that acts in transcription, replication and genome stability. It is required for resistance against genotoxic agents and involved in the repair of DNA double-strand breaks (DSB) by homologous recombination (HR). However, causes underlying the HR defect of INO80-C mutant cells have been controversially discussed. We here unite previous findings using a high-resolution system to study HR in the yeast Saccharomyces cerevisiae. We find that INO80-C has at least two distinct functions during HR, which promote DNA end resection and presynaptic filament formation, respectively. Importantly, specifically the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR.INO80是一种进化保守的核小体重塑复合物，参与转录、复制及基因组稳定性维持过程。其对抵抗遗传毒性试剂不可或缺，同时参与同源重组（homologous recombination, HR）修复DNA双链断裂（DNA double-strand breaks, DSB）的过程。然而，INO80复合物（INO80-C）突变体细胞出现同源重组缺陷的潜在机制长期存在广泛争议。本研究整合既往相关研究成果，借助高分辨率实验体系在酿酒酵母（Saccharomyces cerevisiae）中开展同源重组相关研究。结果表明，INO80复合物在同源重组过程中至少具备两种不同功能，分别促进DNA末端切除与突触前丝形成。尤为关键的是，其第二种功能与组蛋白变体H2A.Z特异性相关。在缺失H2A.Z的情况下，INO80复合物缺陷型突变体的突触前丝形成与同源重组过程得以恢复，这表明突触前丝形成是INO80复合物在同源重组过程中的核心功能。