Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.

Mammalian oocytes and embryos are known to exhibit a markedly low frequency of de novo mutations compared to somatic cells. We still lack efficient tools to carry out functional studies of the intergenerational mechanism of genome protection, and our view of this phenomenon is constantly being modified in light of the new results. Although oocytes were originally considered a cell type lacking DNA repair, new results indicate that mammalian oocytes might possess a set of unique properties that make them and their descendants resistant to accumulation of DNA damage. Here, we review various factors that can influence oocyte and embryo genome stability and discuss the functional evidence for the uniquely efficient response to DNA damage, particularly in the presence of minor DNA lesions and single-strand breaks. We discuss whether high levels of DNA repair proteins might be the basis for the observed low mutation rate. Finally, we present the idea that the unique characteristics of the chromatin landscape, as well as the limited replication, rather than the abundance of repair factors alone, may be responsible for the intergenerational protection of the genome.