A cell culture comparative biology approach to study mechanisms of genome stability and their relevance for species longevity: a newer interpretation of DNA damage induced nuclear foci

The DNA-damage response (DDR) initiates cellular processes that ca lead to DNA repair, senescence or apoptosis. Differences in DDR efficiency may contribute to species-specific differences in lifespan and partially explain the exceptional longevity of some species. To better understand the differences in genomic stability between species, in fibroblast cultures from several mammals, we have examined the appearance of micronuclei and the recruitment of 53BP1 in nuclear structures termed foci, after genotoxic insult represented by Etoposide and Neocarcinostatin. Quantification of 53BP1 foci formation together with micronucleiappearance up to three days after damage showed that cells from long-lived species appear to be better equipped in controlling progression into the cell cycle. This capacity may be the consequence of a better abilityto detect DNA damage. We propose a newer interpretation of nuclear foci. They do not simply represent the presence of DNA damage but rather the cell awareness of it. They do not simply represent the presence of DNA damage but rather the cell awareness of it. We suggest that a key element for species longevity is the capacity to detect damage and to take the necessary time to make an accurate choice between repair, senescence or apoptosis.