DNA Damage Detection by 53BP1: Relationship to Species Longevity

J Gerontol A Biol Sci Med Sci. 2017 Jun 1;72(6):763-770. doi: 10.1093/gerona/glw170.

Abstract

In order to examine potential differences in genomic stability, we have challenged fibroblasts derived from five different mammalian species of variable longevity with the genotoxic agents, etoposide and neocarzinostatin. We report that cells from longer-lived species exhibit more tumor protein p53 binding protein 1 (53BP1) foci for a given degree of DNA damage relative to shorter-lived species. The presence of a greater number of 53BP1 foci was associated with decreased DNA fragmentation and a lower percentage of cells exhibiting micronuclei. These data suggest that cells from longer-lived species have an enhanced DNA damage response. We propose that the number of 53BP1 foci that form in response to damage reflects the intrinsic capacity of cells to detect and respond to DNA harms.

Keywords: 53BP1; DNA damage foci; Genomic stability; Longevity; Micronuclei.

MeSH terms

  • Animals
  • Cattle
  • Cell Cycle Checkpoints
  • Cell Line
  • Chiroptera
  • Cyclin A / metabolism
  • Cytotoxins / toxicity
  • DNA Damage*
  • DNA Fragmentation
  • Dogs
  • Etoposide / toxicity
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Genomic Instability
  • Histones / metabolism
  • Humans
  • Life Expectancy
  • Longevity*
  • Mice
  • Micronuclei, Chromosome-Defective
  • Micronucleus Tests
  • NIMA-Related Kinases / metabolism
  • Topoisomerase II Inhibitors / toxicity
  • Tumor Suppressor p53-Binding Protein 1 / metabolism*
  • Zinostatin / toxicity

Substances

  • Cyclin A
  • Cytotoxins
  • H2AX protein, human
  • Histones
  • Topoisomerase II Inhibitors
  • Tumor Suppressor p53-Binding Protein 1
  • Etoposide
  • Zinostatin
  • NIMA-Related Kinases
  • Nek4 protein, human