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Protein acetylation is mediated by histone acetyltransferases (HATs) and deacetylases (HDACs), which influence chromatin dynamics, protein turnover and the DNA damage response. ATM and ATR mediate DNA damage checkpoints by sensing double-strand breaks and single-strand-DNA-RFA nucleofilaments, respectively. However, it is unclear how acetylation modulates the DNA damage response. Here we show that HDAC inhibition/ablation specifically counteracts yeast Mecl (orthologue of human ATR) activation, double-strand-break processing and single-strand-DNA-RFA nucleofilament formation. Moreover, the recombination protein Sae2 (human CtIP) is acetylated and degraded after HDAC inhibition. Two HDACs, Hda1 and Rpd3, and one HAT, Gcn5, have key roles in these processes. We also find that HDAC inhibition triggers Sae2 degradation by promoting autophagy that affects the DNA damage sensitivity of hda1 and rpd3 mutants. Rapamycin, which stimulates autophagy by inhibiting Tor, also causes Sae2 degradation. We propose that Rpd3, Hda1 and Gcn5 control chromosome stability by coordinating the ATR checkpoint and double-strand-break processing with autophagy., HATs and HDACs target histones and non-histone proteins (1-4) and regulate chromosome dynamics. They also influence the DNA damage response through acetylation of key DNA repair and checkpoint proteins (2). [...]

Rare cells with the properties of stem cells are integral to the development and perpetuation of leukaemias. A defining characteristic of stem cells is their capacity to self-renew, which is [...]

Author(s): Gioacchino Natoli, Saverio Minucci, Pier Giuseppe Pelicci Author Affiliations: Shiftworking keeps locked-down lab on track As researchers in one of the regions most severely affected by COVID-19, we have [...]

Author(s): Mark Pearson [1]; Roberta Carbone [1]; Carla Sebastiani [2]; Mario Cioce [1]; Marta Fagioli [2]; Shin'ichi Saito [3]; Yuichiro Higashimoto [3]; Ettore Appella [3]; Saverio Minucci [1]; Pier Paolo [...]