**12. Conclusion**

*Chronobiology - The Science of Biological Time Structure*

**Light**

**FAD**

**oxidase**

**Flavin containg**

the redox state of cells [67]. Recent studies have provided evidence that flavincontaining oxidases are responsible for the light-dependent production of ROS that are second messengers coupling photoreception to photoreactivation and the

**MAPKs**

**ROS**

**D-box**

**TEF or DBP** *zCry1a, zPer2*

Induction of expression

Activation

**11. Link between circadian clocks and light-dependent DNA repair in** 

Solar radiation has both beneficial and harmful effects for most species. Beneficial aspects include its role in photosynthesis and the entrainment of circadian clocks [28]. However, the UV component of solar radiation can produce cytotoxic, mutagenic, and carcinogenic lesions in DNA, which can transform or kill cells. In particular, the UV component of solar radiation produces cytotoxic and mutagenic lesions in DNA called cyclobutane pyrimidine dimers (CPDs) and pyrimidine [6-4] pyrimidone photoproducts. Photoreactivation is a lightdependent DNA repair mechanism mediated by DNA photolyases (PHRs), which bind to and repair UV-induced DNA damage using visible light as an energy source [43, 68]. Two classes of PHRs have been identified, one specific for CPDs (CPD PHRs) and the other specific for [6-4] photoproducts (64PHRs). Importantly, both the induction of PHRs in response to light and the subsequent light-dependent repair of DNA by PHRs are essential for successful photoreactivation in zebrafish

circadian clock in zebrafish [62, 66] (**Figure 3**).

*Light signaling pathway regulating clock gene induction in zebrafish.*

**zebrafish**

**Figure 3.**

**28**

In mammals, light signals are received by the retina and then integrated with the SCN cellular clocks [7]. The SCN cellular clocks then transmit light information to peripheral cellular clocks via humoral signals and synchronize them. Recent studies have reported that factors other than cellular clocks in the SCN can synchronize peripheral cellular clocks in a light-dependent manner [42]. In contrast, in zebrafish, light directly synchronizes peripheral cellular clocks in addition to central cellular clocks [9]. Despite the differences between the light-dependent regulation of peripheral cellular clocks in mammals and zebrafish, both require similar MAPK signaling pathways and light induction of clock genes to regulate cellular clocks in a light-dependent manner.

The development of circadian clocks would be one way to segregate daytime from nighttime processes, with light-dark cycles acting as selective pressures [28]. In this scenario, increasing levels of oxygen free radicals during the daytime may have been a decisive factor in relegating the anabolic processes of mitosis, growth, and consolidation to the dark hours. Thus, it is reasonable to propose that redox signaling and stress responding pathways such as MAPKs are utilized in the lightdependent regulation of the circadian clock.

### **Acknowledgements**

This work was supported in part by a Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research [19K12900 (J.I.) and 18KT0068 (J.H.)]. This work was also supported by grants from the Watanabe Foundation and the Smoking Research Foundation (J.H.).
