TP53 is not required for the constitutive or induced repair of DNA damage produced by ionizing radiation at the G(1)/S-phase border

We have previously described a novel DNA repair response that is induced in cells irradiated with ionizing radiation at the G(1)/S-phase border and is characterized by the formation of very long repair patches (VLRP) containi ng at least 150 nucleotides. In the current study, we examined whether ther e is a requirement for TP53 in this induced repair process. We find that in normal cells, the endogenous levels of TP53 are elevated at the G(1)/S-pha se border, and that these levels are not further increased after irradiatio n with 5 Gy, In cells expressing the ES oncoprotein of human papillomavirus , which inactivates TP53 function, there is a greatly accentuated induction of the VLRP that nearly masks the constitutive repair response. Incubation of cells in the presence of cycloheximide, which inhibits the induced repa ir, reveals the presence of the constitutive repair patches. Ail cells exam ined continue to replicate their DNA after exposure to ionizing radiation. In contrast, cells irradiated with UV radiation at the G(1)/S-phase border show an induction of TP53 protein and halt DNA synthesis, but do not induce the VLRP, Our results show that TP53 is not required for the constitutive or induced repair of DNA damage induced by ionizing radiation. In addition, these results suggest that TP53 may suppress the formation of VLRP and tha t the progression of cells through S phase after exposure to ionizing radia tion signals the induced repair response, (C) 1999 by Radiation Research So ciety.