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

Abstract

ABSTRACTChromatin 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.Key Points-NuA4-dependent acetylation modulates nucleosome dynamics to assist DNA end resection and strand invasion during homologous recombination.-Combined recruitment and local action of NuA4 and SAGA acetyltransferase complexes is essential for DNA end resection.-Cooperation between NuA4 and SAGA acetyltransferases is required for homologous recombination in eukaryotes.