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Role and Regulation of p53 during an Ultraviolet Radiation-induced G₁ Cell Cycle Arrest¹

Harvard School of Public Health, Department of Cancer Cell Biology, Boston, Massachusetts 02115

p53 can play a key role in response to DNA damage by activating a G₁ 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-deficient cells to examine the role and regulation of p53 in response to UV radiation. A dose-dependent G₁ arrest was observed in normal and repair-deficient cells exposed to UV. Expression of HPV16-E6, or a dominant-negative p53 mutant that inactivates wild-type p53, caused cells to become resistant to this UV-induced G₁ arrest. However, a G₁ to S-phase delay was still observed after UV treatment of cells in which p53 was inactivated. These results indicate that UV can inhibit G₁ to S-phase progression through p53-dependent and independent mechanisms. Cells deficient in the repair of UV-induced DNA damage were more susceptible to a G₁ arrest after UV treatment than cells with normal repair capacity. Moreover, no G₁ arrest was observed in cells that had completed DNA repair prior to monitoring their movement from G₁ into S-phase. Finally, p53 was stabilized under conditions of a UV-induced G₁ arrest and unstable when cells had completed DNA repair and progressed from G₁ into S-phase. These results suggest that unrepaired DNA damage is the signal for the stabilization of p53, and a subsequent G₁ phase cell cycle arrest in UV-irradiated cells.

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