Dear Editor,

The DNA damage response (DDR) ensures repair of DNA lesions caused by endogenous and exogenous mutagens that constantly threaten genomic integrity. Defective DDR results in accumulation of DNA lesions that could potentially lead to genomic instability and tumorigenesis. Posttranslational modifications (PTMs) including phosphorylation, methylation, acetylation, ubiquitination, and sumoylation play a central role in sensing, signaling, and repairing damaged DNA. Currently, it remains unknown whether lysine crotonylation (Kcr) is implicated in DDR. Kcr is an evolutionary conserved and abundant PTM that occurs in all core histones, and it promotes gene expression, at least in part, by providing binding sites to Yaf9, ENL, AFL, Taf14, Sas5 (YEATS) domain- containing proteins (Tan et al., 2011; Li et al., 2016). In addition, it was shown that hundreds of nonhistone proteins implicated in various biological processes, such as RNA processing and gene expression, undergo crotonylation at their lysine residues (Xu et al., 2017). Similar to acetylation, Kcr is a reversible modification that is catalyzed by the activity of p300 `writer’ protein and removed predominantly by class I histone deacetylases (HDACs) ‘eraser’ proteins. Furthermore, it was reported that sirtuin family deacetylases (SIRT1-3) exhibit modest decrotonylase activity (Wei et al., 2017).