Genomic instability in F1 mice born to irradiated spermatozoa and p53 dependent genomic cross-talk

Abstract

Radiation induced genomic instability is characterized by two features; untargeted and delayed mutation. We have shown that irradiation of sperm results in induction of maternal allele mutation at a minisatellite and the pink-eyed locus in F1 mice. Detailed analysis of embryos fertilized by irradiated sperm indicated that DNA synthesis of both male and female pronuclei is suppressed p53 dependently. This p53 dependent S checkpoint operates also in tissue culture cells. In the cells irradiated with less than 2.5 Gy, p53 aids ATM dependent phosphorylation of PCNA which then slows down the replication fork movement. Under this condition, PCNA forms foci in irradiated cells. In the absence of p53, PCNA was distributed in the nucleus homogeneously and DNA replication progresses at a rate equivalent to that of unirradiated cells. The relation between slowing-down of replication fork and recombination will be discussed. [J Radiat Res 44:375 (2003)]