Chromatin modifying complexes play important yet not fully defined roles in DNA repair processes. The essential NuA4 histone acetyltransferase (HAT) complex is recruited to double-strand break (DSB) sites and spreads along with DNA end resection. As predicted, NuA4 acetylates surrounding nucleosomes upon DSB induction and defects in its activity correlate with altered DNA end resection and Rad51 recombinase recruitment. Importantly, we show that NuA4 is also recruited to the donor sequence during recombination along with increased H4 acetylation, indicating a direct role during strand invasion/D-loop formation after resection. We found that NuA4 cooperates locally with another HAT, the SAGA complex, during DSB repair as their combined action is essential for DNA end resection to occur. This cooperation of NuA4 and SAGA is required for recruitment of ATP-dependent chromatin remodelers, targeted acetylation of repair factors and homologous recombination. Our work reveals a multifaceted and conserved cooperation mechanism between acetyltransferase complexes to allow repair of DNA breaks by homologous recombination.

中文翻译：

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NuA4和SAGA乙酰基转移酶复合物通过同源重组协同修复DNA断裂

染色质修饰复合物在DNA修复过程中起着重要但尚未完全定义的作用。必需的NuA4组蛋白乙酰基转移酶（HAT）复合物被募集到双链断裂（DSB）位点，并随DNA末端切除一起扩散。如预期的那样，NuA4在DSB诱导后会乙酰化周围的核小体，其活性缺陷与DNA末端切除和Rad51重组酶募集改变有关。重要的是，我们显示NuA4在重组过程中也被募集到供体序列中，同时H4乙酰化程度增加，这表明在切除后链侵袭/ D环形成过程中具有直接作用。我们发现，在DSB修复过程中，NuA4与另一个HAT SAGA复合体在局部协同作用，因为它们的联合作用对于发生DNA末端切除至关重要。NuA4和SAGA的这种合作对于募集ATP依赖的染色质重塑剂，修复因子的靶向乙酰化和同源重组是必需的。我们的工作揭示了乙酰转移酶复合物之间的多方面且保守的协作机制，以允许通过同源重组修复DNA断裂。