Evasion of UVC-induced apoptosis by photorepair of cyclobutane pyrimidine dimers.

Cyclobutyl pyrimidine dimer (CPD) photolyase is known to reverse pyrimidine dimers specifically under illumination with visible light. OCP13, a Medaka cell line showing a high level expression of the gene for CPD photolyase, completely reversed pyrimidine dimers induced by 20 J/m2 UVC by 1 h of photorepair. When OCP13 cells were irradiated with 20 J/m2 UVC, morphological changes such as shrinkage of cells, distorted nuclear shape, and decrease in the number of nucleoli appeared 2 to 4 h after UVC irradiation. Thereafter, the irradiated cells began to detach from the substratum, and DNA ladders were observed in the DNA extracted from detached cells. Thus, these changes in cells after UVC exposure were used to characterize the progression of UV-induced apoptosis in OCP13 cells. Although formation of DNA ladders and cell detachment were blocked by cycloheximide treatment prior to UVC exposure, the morphological changes were not. With photorepair treatment, even after the morphological changes appeared cells were still able to restore their normal morphological features and remained attached. On the other hand, the cell-cycle progression in UVC-irradiated cells was arrested even after photorepair of pyrimidine dimers. Thus, photorepair can rescue cells from UV-induced apoptosis, although DNA damage other than that of pyrimidine dimers, as well as additional non-DNA damage, possibly remained, and DNA replication was left inhibited. Among the various kinds of damage induced by UVC irradiation, the presence of pyrimidine dimers is proposed to be the major trigger for UVC-induced apoptosis.