Poly(ADP-ribosyl)ation: A Posttranslational Protein Modification Linked With Genome Protection and Mammalian Longevity

Biogerontology. 2000;1(1):41-6. doi: 10.1023/a:1010089924898.

Abstract

Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins catalysed by the 113-kDa enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and, to a lesser extent, by several other recently described polypeptides. The catalytic function of PARP-1 is directly stimulated by DNA strand breaks, thus making poly(ADP-ribosyl)ation one of the immediate cellular responses to oxidative and other types of DNA damage. Poly(ADP-ribosyl)ation plays an important role in the recovery of proliferating cells from certain types of DNA damage, and this has been linked mechanistically with an involvement in DNA base-excision repair. Furthermore PARP-1 activity is necessary to maintain genomic stability under conditions of genotoxic stress and is actually a key regulator of alkylation-induced sister-chromatid exchange formation, imposing a control that is strictly negative and commensurate with the enzyme activity level. Finally, there is a positive correlation between the poly(ADP-ribosyl)ation capacity of mononuclear leukocytes of various mammalian species and species-specific life span. Likewise, lymphoblastoid cell lines derived from human centenarians display a higher poly(ADP-ribosyl)ation capacity than controls. In conclusion, PARP-1 may be viewed as a factor that is responsible for downregulating the rate of genomic instability events, which are provoked by the constant attack by endogenous and exogenous DNA-damaging agents, in such a way as to tune them to a level which is just appropriate for the life span potential of a given species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics*
  • Aging / metabolism*
  • Animals
  • DNA Damage*
  • Genome
  • Humans
  • Longevity / genetics
  • Longevity / physiology
  • Mammals
  • Nuclear Proteins / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Processing, Post-Translational*
  • Telomere

Substances

  • Nuclear Proteins
  • Poly(ADP-ribose) Polymerases