A baculovirus photolyase with DNA repair activity and circadian clock regulatory function.
Cryptochromes and photolyases belong to the same family of flavoproteins but, despite being structurally conserved, display distinct functions. Photolyases use visible light to repair ultraviolet-induced DNA damage. Cryptochromes, however, function as blue-light receptors, circadian photoreceptors, or repressors of the CLOCK/BMAL1 heterodimer, the transcription activator controlling the molecular circadian clock. Here, we present evidence that the functional divergence between cryptochromes and photolyases is not so univocal. Chrysodeixis chalcites nucleopolyhedrovirus possesses 2 photolyase-like genes: phr1 and phr2. We show that PHR1 and PHR2 are able to bind the CLOCK protein. Only for PHR2, however, the physical interaction with CLOCK represses CLOCK/BMAL1-driven transcription. This result shows that binding of photolyase per se is not sufficient to inhibit the CLOCK/BMAL1 heterodimer. PHR2, furthermore, affects the oscillation of immortalized mouse embryonic fibroblasts, suggesting that PHR2 can regulate the molecular circadian clock. These findings are relevant for further understanding the evolution of cryptochromes and photolyases as well as behavioral changes induced in insects by baculoviruses.
Laboratory of Virology, Wageningen University, Wageningen, the Netherlands.
Magdalena A
MA
Biernat
André P M
AP
Eker
Monique M
MM
van Oers
Just M
JM
Vlak
Gijsbertus T J
GT
van der Horst
Inês
I
Chaves
D056930:ARNTL Transcription Factors / Q000037:antagonists & inhibitors; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism*; D057906:Circadian Clocks / Q000187:drug effects; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D017924:Nucleopolyhedroviruses / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D056926:CLOCK Proteins; D004255:Deoxyribodipyrimidine Photo-Lyase; C572430:phr2 enzyme, Chrysodeixis chalcites nucleopolyhedrovirus