Class II HDAC Clr3-mediated H2B deacetylation promotes DNA damage and replication stress response in Schizosaccharomyces pombe.

DNA damage and replication stress cause genome instability. Histone H3/H4 deacetylation by class I histone deacetylases (HDACs) and H3 methylation by histone methyltransferases promote DNA repair and fork stability. However, other histone modifications and enzymes involved remain unclear. Here, in the fission yeast Schizosaccharomyces pombe, we found that histone H2B N-terminal K5, K10, and K15 residues were deacetylated by the class II HDAC Clr3 under DNA damage and replication stress. Clr3 or SHREC was recruited to DNA breaks and stressed forks by interacting with Rad9-Rad1-Hus1. H2B hyperacetylation and Clr3 loss disrupted chromatin compaction, impaired sister chromatid cohesion, suppressed Rad51 loading and homologous recombination, and exhibited genotoxic sensitivities. Our findings reveal a novel role for H2B deacetylation by class II HDACs in genome stability.