Abstract
Absorption of solar ultraviolet (UV) radiation by DNA leads to the formation of the highly mutagenic cyclobutane pyrimidine dimer (CPD). The mutagenicity of CPD is caused, in part, by the fact that their recognition and repair by the nucleotide excision repair (NER) pathway is challenging and slow. It has been previously shown that a pre-stimulation with genotoxic agents improve NER efficiency of CPD, indicating a potential adaptive response of this repair pathway. We have pre-treated human dermal fibroblasts with repeated subletal low doses of UVB (chronic low-dose of UVB; CLUV) to determine whether it could enhance NER capacity to repair CPD. Our results show that CLUV pre-treatment greatly enhances CPD repair but have little effect on the repair of another UV-induced bypirimidine photoproduct, the pyrimidine (6-4) pyrimidone photoproducts (6-4 PP). We have determined that the CLUV treatment activates p53 and we found an increase of DDB2 and XPC gene expression. This is consistent with an increasing level of NER recognition proteins, DDB2 and XPC, we found concentrated at the chromatin. This study represents the first demonstration that chronic UVB exposure can stimulate NER pathway. Altogether, these results shed light on the potential adaptability of the NER by chronic UVB irradiation and the mechanisms involved.