INDUCTION OF P53 IN MOUSE CELLS DECREASES MUTAGENESIS BY UV-RADIATION

The tumor supressor protein, p53, is proposed to have a critical role in maintaining the integrity of the genetic material. It has been esta blished that p53 induces a cell cycle block in the G1 phase upon cellu lar DNA damage. Recent evidence also indicates the involvement of p53 directly and indirectly in nucleotide excision repair (NER). We have e xamined the role of p53 with respect to UV-induced mutagenesis. By gen e transfer, we established a mouse fibroblast cell line overexpressing the val(135) temperature-sensitive p53 allele. In this line, p53 acti vity can be modulated through temperature shift, as confirmed by Weste rn blot and by cell cycle analysis. This cell line was also constructe d to contain a recoverable lambda phage shuttle vector carrying the su pF mutation reporter gene. Induction of p53 was found to enhance the c lonogenic survival of the cells follo,wing UV-irradiation compared to the p53-deficient parental mouse cell line. The transfectant line also displayed a 4-fold reduction in the frequency of W-induced mutations as measured in the chromosomally integrated supF reporter gene. Our re sults are consistent with a p53-induced cell cycle block at G1 allowin g cells to repair chromosomal damage before DNA replication. However, our data may also reflect a more direct role of p53 in the repair of U V-induced lesions as suggested by studies showing that p53 can interac t directly with repair factors.