Multiple DNA repair pathways collectively protect against DNA damage-induced replicative aging.

We demonstrate that transcriptomic profiling of the NER mutant ercc-1 offers better understanding of the complex phenotypes of ercc-1 deficiency in C. elegans, as it does in mammalian models. There is a transcriptomic shift in ercc-1 mutants that suggests a stochastic impairment of growth and development, with a shift towards a higher proportion of males in the population. Extensive phenotypic analyses confirm that NER deficiency in C. elegans leads to severe developmental and growth defects and a reduced replicative lifespan, although post-mitotic lifespan is not affected. Results suggest that these defects are caused by an inability to cope with randomly occurring DNA damage, which may interfere with transcription and replication.

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Lans H, Lindvall JM, Thijssen K, Karambelas AE, Cupac D, Fensgård O, Jansen G, Hoeijmakers JH, Nilsen H, Vermeulen W