In vivo repair of alkylating and oxidative DNA damage in the mitochondrial and nuclear genomes of wild-type and glycosylase-deficient Caenorhabditis elegans

► We measured repair of oxidative and alkylating DNA damage in vivo in the mitochondrial and nuclear genomes of C. elegans. ► Base excision repair of both types of damage in both genomes was comparable to what has been observed in mammals. ► H2O2 caused more mitochondrial than nuclear DNA damage, but the reverse occurred with methylmethanesulfonate (MMS). ► A deletion in the nth-1 glycosylase gene did not reduce DNA repair or sensitize C. elegans to exposure to H2O2 or MMS. Base excision repair (BER) is an evolutionarily conserved DNA repair pathway that is critical for repair of many of the most common types of DNA damage generated both by endogenous metabolic pathways and exposure to exogenous stressors such as pollutants. Caenorhabditis elegans is an increasingly important model organism for the study of DNA damage-related processes including DNA repair, genotoxicity, and apoptosis, but BER is not well understood in this organism, and has not previously been measured in vivo. We report robust BER in the nuclear genome and slightly slower damage removal from the mitochondrial genome; in both cases the removal rates are comparable to those observed in mammals. However we could detect no deficiency in BER in the nth-1 strain, which carries a deletion in the only glycosylase yet described in C. elegans that repairs oxidative DNA damage. We also failed to detect increased lethality or growth inhibition in nth-1 nematodes after exposure to oxidative or alkylating damage, suggesting the existence of at least one additional as-yet undetected glycosylase.