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Poly(ADP-ribosyl)ation: A posttranslational protein modification linked with genome protection and mammalian longevity

Lookup NU author(s): Professor Alexander Burkle


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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. © 2000 Kluwer Academic Publishers.

Publication metadata

Author(s): Burkle A

Publication type: Review

Publication status: Published

Journal: Biogerontology

Year: 2000

Volume: 1

Issue: 1

Pages: 41-46

Print publication date: 01/01/2000

ISSN (print): 1389-5729

ISSN (electronic): 1573-6768


PubMed id: 11707919