**5. Posttranslational modifications contributing to both the circadian clock regulation and the cellular DDR**

Posttranslational modifications of proteins regulate various biological processes at molecular levels, including gene expression, chromatin remodeling, and protein stabilization. These molecular events have essential roles in appropriately regulating biological phenomena, including development and circadian clock, by maintaining cellular functions, such as proliferation and molecular clocks, respectively. Posttranslational modifications, such as phosphorylation, sumoylation, and acetylation, control the transcriptional activity, subcellular localization, and stability of circadian clock regulators in multiple ways [4, 33]. In particular, the defects in phosphorylating the circadian clock regulators have been implicated in human sleep disorders [34, 35]. It is also well established that posttranslational modifications are vital for the regulation of the cell cycle and DDR. SIRT1 and casein kinase2 (CK2), already identified as responsible factors for posttranslational modifications of clock proteins [18, 36–39], have also been implicated in posttranslational modifications of proteins such as p53, forkhead box class O (FoxO), and E-cadherin that are involved in cellular metabolism, the cell cycle, and DDR [40, 41]. These findings support the hypothesis that the circadian clocks may be linked to other cellular processes, such as cell cycle control and DDR, through shared posttranslational modifications.
