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

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

**29**

*Light-Dependent Regulation of Circadian Clocks in Vertebrates*

evolutionary link between the circadian clock and DNA repair.

cells [21]. Notably, the expression level of the *z64Phr* gene is regulated by the same light-induced MAPK cascades as those controlling the expression of the clock gene *zCry1a*, which is associated with the light-dependent regulation of the circadian clock [21, 66]. Light-induced ERK activation triggers the expression of *z64Phr*, whereas light-induced p38 activation inhibits it. Thus, both light-dependent DNA repair and regulation of the circadian clock are governed by shared regulatory pathways. Both CRYs and PHRs belong to the DNA photolyase/cryptochrome protein family and have highly similar amino acid sequences [43, 68]. Evolutionary studies have shown that the animal CRY protein functionally diverged first from the CPD photolyase and then further to generate 64PHR [69]. These facts, together with the observation that *zCry1a* and *z64Phr* share regulatory pathways, strongly indicate an

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

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 light-

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

*DOI: http://dx.doi.org/10.5772/intechopen.86524*

**12. Conclusion**

light-dependent manner.

**Acknowledgements**

dependent regulation of the circadian clock.

Smoking Research Foundation (J.H.).

*Light-Dependent Regulation of Circadian Clocks in Vertebrates DOI: http://dx.doi.org/10.5772/intechopen.86524*

cells [21]. Notably, the expression level of the *z64Phr* gene is regulated by the same light-induced MAPK cascades as those controlling the expression of the clock gene *zCry1a*, which is associated with the light-dependent regulation of the circadian clock [21, 66]. Light-induced ERK activation triggers the expression of *z64Phr*, whereas light-induced p38 activation inhibits it. Thus, both light-dependent DNA repair and regulation of the circadian clock are governed by shared regulatory pathways. Both CRYs and PHRs belong to the DNA photolyase/cryptochrome protein family and have highly similar amino acid sequences [43, 68]. Evolutionary studies have shown that the animal CRY protein functionally diverged first from the CPD photolyase and then further to generate 64PHR [69]. These facts, together with the observation that *zCry1a* and *z64Phr* share regulatory pathways, strongly indicate an evolutionary link between the circadian clock and DNA repair.
