A cell culture comparative biology approach to study mechanisms of genomic stability and their relevance for species longevity: a newer interpretation of 53BP1 nuclear foci

The DNA-damage response (DDR) is crucial for the maintenance of DNA integrity and genomic stability. Differences in the DDR efficiency may contribute to species-specific differences in lifespan and partially explain the exceptional longevity of some species. To better understand differences in genomic stability between species, we have examined the appearance of micronuclei (MN) and the recruitment of 53BP1 in nuclear structures, termed foci, in primary fibroblasts from five different mammals treated with two genotoxic agents which induce double strand breaks (DBS): Etoposide and Neocarcinostatin. Quantification of 53BP1 foci formation up to 3 days after damage shows an inverse correlation with micronuclei appearance: across the five examined species, lower percentage of 53BP1 foci is associated with increasing level of MN. This correlation suggests that cells from long-lived species appear to be better equipped in DNA damage controlling the progression into the cell cycle. We propose a newer interpretation of 53BP1 nuclear foci. 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.