Role and regulation of p53 during an ultraviolet radiation-induced G(1) cell cycle arrest

p53 can play a key role in response to DNA damage by activating a G(1) cell cycle arrest, However, the importance of p53 in the cell cycle response to UV radiation is unclear, In this study, we used normal and repair-deficien t cells to examine the role and regulation of p53 in response to UV radiati on. A dose-dependent G(1) arrest was observed in normal and repair-deficien t cells exposed to UV. Expression of HPV16-E6, or a dominant-negative p53 m utant that inactivates wildtype p53, caused cells to become resistant to th is UV-induced G(1) arrest. However, a G(1) to S-phase delay was still obser ved after UV treatment of cells in which p53 was inactivated, These results indicate that UV can inhibit G(1) to S-phase progression through p53-depen dent and independent mechanisms, Cells deficient in the repair of UV-induce d DNA damage were more susceptible to a G(1) arrest after UV treatment than cells with normal repair capacity, Moreover, no G(1) arrest was observed i n cells that had completed DNA repair prior to monitoring their movement fr om G(1) into S-phase, Finally, p53 was stabilized under conditions of a UV- induced G(1) arrest and unstable when cells had completed DNA repair and pr ogressed from G(1) into S-phase, These results suggest that unrepaired DNA damage is the signal for the stabilization of p53, and a subsequent G(1) ph ase eel cycle arrest in UV-irradiated cells.