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Our findings reveal that H3K56ac alone induces considerable disturbance to the histone-DNA/histone-histone interactions, and amplifies the distortions imposed by the presence of the lesion. Our work highlights the important role of H3K56 acetylation in response to DNA damage and depicts how access to DNA lesions by the repair machinery can be facilitated within the nucleosome via a key acetylation event.The accurate repair of DNA damage specifically the chromosomal double-strand breaks (DSBs) arising from exposure to physical or chemical