The Caenorhabditis elegans
rad-3 gene was identified in a genetic screen for radiation sensitive (rad) mutants. Here, we report that the UV sensitivity of
rad-3 mutants is caused by a nonsense mutation in the C. elegans orthologue of the human nucleotide excision repair gene XPA. We have used the
xpa-1/rad-3 mutant to examine how a defect in nucleotide excision repair (NER) perturbs development. We find that C. elegans carrying a mutation in
xpa-1/rad-3 are hypersensitive and hypermutable in response to UV irradiation, but do not display hypersensitivity to oxidative stress or show obvious developmental abnormalities in the absence of UV exposure. Consistent with these observations, non-irradiated
xpa-1 mutants have a similar lifespan as wild type. We further show that UV irradiated
xpa-1 mutants undergo a stage-dependent decline in growth and survival, which is associated with a loss in transcriptional competence. Surprisingly, transcriptionally quiescent dauer stage larvae are able to survive a dose of UV irradiation, which is otherwise lethal to early stage larvae. We show that the loss of transcriptional competence in UV irradiated
xpa-1 mutants is associated with the degradation of the large RNA polymerase II (RNA pol II) subunit, AMA-1, and have identified WWP-1 as the putative E3 ubiquitin ligase mediating this process. The absence of
wwp-1 by itself does not cause sensitivity to UV irradiation, but it acts synergistically with a mutation in
xpa-1 to enhance UV hypersensitivity.