Like father like son: Transgenerational Genomic Instability in Mammals

by Yuri E Dubrova (University of Leicester)

Thursday 24 Feb 2011, 12:30 → 13:30 Europe/Stockholm

CCK R8:00 (CCK R8:00)

LIKE FATHER LIKE SON: Transgenerational Genomic Instability in Mammals Speaker: Professor Yuri E Dubrova, Department of Genetics, University of Leicester, United Kingdom. yed2@le.ac.uk Mutation induction in the directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation and chemical mutagens. However, recent data on the delayed effects of exposure to ionizing radiation represent a new challenge to the existing paradigm. The results of numerous in vitro studies show that ionizing radiation can not only induce mutations in the directly exposed cells, but can also lead to delayed effects, with new mutations arising many cell divisions after the initial irradiation damage. Apart from the studies on mutation rates in somatic cells, considerable progress has been made in the analysis of radiation-induced instability in the mammalian germline, where the effects of radiation exposure were investigated among the offspring of irradiated parents. Our results show that mutation rates at tandem repeat DNA loci and protein-coding genes are substantially elevated in the germline and somatic tissues of non-exposed offspring of irradiated male mice. According to our data, this remarkable transgenerational destabilization can be attributed to the presence of a subset of endogenous DNA lesions. We have recently shown that paternal treatment by the alkylating agent ethylnitrosourea also results in the transgenerational effects, thus implying that this phenomenon is not initiated by a specific sub-set of DNA lesions and is most probably triggered by a stress-like response to a generalized DNA damage. Our data imply that instability detected in the non-exposed offspring is caused by some DNA-dependent signal transmitted from the irradiated father and implicate an epigenetic mechanism for the transgenerational instability. The potential implication of these results for the estimates of genetic risks for humans will be discussed.