Lademann Claudio A, Renkawitz Jörg, Pfander Boris, Jentsch Stefan
Molecular Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Cell Rep. 2017 May 16;19(7):1294-1303. doi: 10.1016/j.celrep.2017.04.051.
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR-DNA end resection and presynaptic filament formation. Importantly, 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复合物（INO80-C）是一种在进化上保守的核小体重塑因子，作用于转录、复制和基因组稳定性。它是抵抗基因毒性试剂所必需的，并且通过同源重组（HR）参与DNA双链断裂（DSB）的修复。然而，INO80-C突变细胞中HR缺陷的原因存在争议。在这里，我们利用一个系统在芽殖酵母中以高空间分辨率研究HR，整合了先前的研究结果。我们发现INO80-C在HR-DNA末端切除和突触前丝形成过程中至少具有两种不同的功能。重要的是，第二种功能与组蛋白变体H2A.Z相关。在缺乏H2A.Z的情况下，INO80-C缺陷型突变体中的突触前丝形成和HR得以恢复，这表明突触前丝形成是INO80-C在HR过程中的关键功能。
