Thymidine dinucleotide mimics the effect of solar simulated irradiation onp53 and p53-regulated proteins

The tumor suppressor protein p53 participates in DNA repair and cell cycle regulation in response to injuries like ultraviolet (UV) irradiation. We ha ve previously reported that the thymidine dinucleotide (pTpT), a common tar get for DNA photoproduct formation by UV Light, mimics many effects of UV i rradiation in cultured skin-derived cells, at least in part through the act ivation of p53. In this report we compare the effects of solar-simulated ir radiation and pTpT on p53 and p53-regulated proteins involved in cellular g rowth arrest and DNA repair in cultured human dermal fibroblasts. We find t hat, like UV irradiation, pTpT increases the levels of p53, p21, and prolif erating-cell nuclear antigen. The magnitude and time course of the inductio ns are UV dose dependent and consistent with known regulatory interactions among these nuclear proteins. These data confirm and expand previous studie s of UV effects on nuclear proteins involved in cell cycle regulation and D NA repair. Our observations suggest that such protective effects can also b e induced by pTpT in the absense of initial DNA damage, rendering cells mor e capable of responding to subsequent DNA damage.