Acetylation of H3K56 orchestrates UV-responsive chromatin events that generate DNA accessibility during Nucleotide Excision Repair

Histone modifications have long been related to DNA damage response. Nucleotide excision repair pathway that removes helix-distorting lesions necessitates DNA accessibility through chromatin modifications. Previous studies have linked H3 tail residue acetylation to UV-induced NER. Here we present evidences that acetylation of H3K56 is crucial for early phases of NER. Using H3K56 mutants K56Q and K56R, which mimic acetylated and unacetylated lysines respectively, we show that recruitment of the repair factor Rad16, a Swi/Snf family member is dependent on H3K56 acetylation. With constitutive H3K56 acetylation, Rad16 recruitment became UV independent. Furthermore, H3K56 acetylation promoted UV-induced hyperacetylation of H3K9 and H3K14. Importantly, constitutive H3K56 acetylation prominently increased chromatin accessibility. During NER, lack of H3K56 acetylation that effectively aborted H3 tail residue acetylation and Rad16 recruitment, thus failed to impart essential chromatin modulations. The NER-responsive oscillation of chromatin structure observed in wild type, was distinctly eliminated in absence of H3K56 acetylation. In vitro assay with wild type and H3K56 mutant cell extracts further indicated that absence of H3K56 acetylation negatively affected DNA relaxation during NER. Overall, H3K56 acetylation regulates Rad16 redistribution and UV-induced H3 tail residue hyperacetylation, and the resultant modification code promotes chromatin accessibility and recruitment of subsequent repair factors during NER.