Combined loss of three DNA damage response pathways renders C. elegans intolerant to light

Publication date: Available online 14 April 2017
Source:DNA Repair
Author(s): Ivo van Bostelen, Marcel Tijsterman
Infliction of DNA damage initiates a complex cellular reaction − the DNA damage response − that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal a surprisingly simple, straightforward, linear order of events for how a simple multicellular eukaryote, C. elegans, deals with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common.



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