p53 Dependency of Delayed and Untargeted Recombination in Mouse Embryos Fertilized by Irradiated Sperm

Abstract

Radiation induction of genomic instability has been demonstrated in whole-animal systems. Although the molecular mechanisms underlying the induced genomic instability are not known at present, this phenomenon could be regarded as the manifestation of a cellular fail-safe system in which fidelity of repair and replication is downregulated to tolerate DNA damage. Two features of genomic instability, namely, delayed mutation and untargeted mutation, require mechanisms for ``damage memory{''} and for ``damage sensing, signal transduction and execution{''} to induce mutations at a nondamaged site. In this chapter, the phenomenon of transgenerational genomic instability and possible mechanisms are discussed using mouse data collected in our laboratory as the main bases.