Because HDAC1 and HDAC2 deacetylate H4K16 to promote DSB repair [49], it is tempting to speculate that the observed HDAC1/HDAC2 overexpression and hypoacetylated H4K16 in cancers could deregulate the DDR, resulting in genetic and epigenetic instability that would promote tumorigenesis [137,138]. This evidence concerns the gene HDAC2 and cancer.