title: Role of wild type p53 in the G2 phase: regulation of the gamma-irradiation-induced delay and DNA repair.
abstract: Upregulation of the p53 protein was shown to induce cell cycle arrest at the G1/S border and in some cases at the G2/M border. Furthermore, it was suggested that p53 is associated with the induction of the various DNA repair pathways. Previously, we demonstrated that cells co-expressing endogenous wild type p53 protein, together with dominant negative mutant p53, exhibit deregulation of apoptosis, G1 arrest and delay in G2 following gamma-irradiation. In the present study, we investigated the role of p53 protein in the DNA damage response at the G2 phase. Using p53-null, wild type p53 and mutant p53-producer cell lines, we found that the two C-terminally spliced p53 forms could prevent gamma-irradiation induced mutagenesis prior to mitosis, at the G2/M checkpoint. We found that at the G2 phase, p53 may facilitate repair of DNA breaks giving rise to micronuclei, and regulate the exit from the G2 checkpoint. At the G1 phase, only the regularly spliced form of p53 caused growth arrest. In contrast, both the regularly and the alternatively spliced p53 forms directed postmitotic micronucleated cells towards apoptosis. These results provide a functional explanation for the cell cycle-independent expression of p53 in normal cycling cells, as well as in cells where p53 is up-regulated, following DNA damage.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
authors.forename: N
authors.initials: N
authors.lastname: Almog
authors.forename: A
authors.initials: A
authors.lastname: Peled
authors.forename: N
authors.initials: N
authors.lastname: Goldfinger
authors.forename: V
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase / Q000528:radiation effects*; D005720:Gamma Rays; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53