NuA4 and SAGA acetyltransferase complexes cooperate for repair of DNA breaks by homologous recombination.

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. Author summary: DNA double strand breaks (DSBs) are among the most dangerous types of DNA lesions as they can produce genomic instability that leads to cancer and genetic diseases. It is therefor crucial to understand the precise molecular mechanisms used by cells to detect and repair this type of damages. Homologous recombination using sister chromatid as template is the most accurate pathway to repair these breaks but has to occur within the context of the DNA compacted structure in chromosomes. Here, we show that two enzymes, NuA4 and SAGA, that acetylate the structural components of chromosomes in the vicinity of the DNA breaks are together essential for recombination-mediated repair to occur. We found that they are recruited at an early step after damage detection and their action allows subsequent remodeling of local structural organisation by other enzymes, providing DNA access to the recombination machinery. These results highlight the cooperation of enzymes for a same goal, providing robustness in the repair process as only the loss of both leads to major defects. [ABSTRACT FROM AUTHOR]