Long lived species appear to have a better control of cell cycle progression in the presence of DNA damage: possible role of 53BP1

Activation of DNA-damage response (DDR) is a crucial process for the maintenance of genomic stability. DDR activation initiates cellular processes that can lead to apoptosis, cell-cycle arrest, DNA repair and cellular senescence. Differences in the DDR efficiency and in the DNA damage sensing machinery may contribute to species-specific differences in lifespan and partially explain the exceptional longevity of some species, like human. To better understand the differences in genomic stability and in damage response pathways 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 a genotoxic insult. We used Etoposide, a hemotherapeutic agents that forms a ternary complex with DNA and the topoisomerase II enzyme and prevents re-ligation of the DNA strands causing DNA breaks. Quantification of 53BP1 foci formation together with micronuclei appearance up to three days after damage showed that cells from long lived species appear better equipped to control progression into the cell cycle. This capacity may be the consequence of a better capacity to detect DNA damage. We propose that a key element for a long lived species is the capacity of cells to take their time to repair the endured damage and to make accurate choices regarding their destiny: proliferation, senescence or apoptosis.