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Poly(ADP-ribosyl)ation: a posttranslational proteinmodification linked with genome protection andmammalian longevity

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Abstract

Poly(ADP-ribosyl)ation is a posttranslationalmodification of nuclear proteins catalysed by the113-kDa enzyme poly(ADP-ribose) polymerase-1 (PARP-1)and, to a lesser extent, by several other recentlydescribed polypeptides. The catalytic function ofPARP-1 is directly stimulated by DNA strand breaks,thus making poly(ADP-ribosyl)ation one of theimmediate cellular responses to oxidative and othertypes of DNA damage. Poly(ADP-ribosyl)ation plays animportant role in the recovery of proliferating cellsfrom certain types of DNA damage, and this has beenlinked mechanistically with an involvement in DNAbase-excision repair. Furthermore PARP-1 activity isnecessary to maintain genomic stability underconditions of genotoxic stress and is actually a keyregulator of alkylation-induced sister-chromatidexchange formation, imposing a control that isstrictly negative and commensurate with the enzymeactivity level. Finally, there is a positivecorrelation between the poly(ADP-ribosyl)ationcapacity of mononuclear leukocytes of variousmammalian species and species-specific life span.Likewise, lymphoblastoid cell lines derived from humancentenarians display a higher poly(ADP-ribosyl)ationcapacity than controls. In conclusion, PARP-1 may beviewed as a factor that is responsible for downregulating therate of genomic instability events, which are provokedby the constant attack by endogenous and exogenousDNA-damaging agents, in such a way as to tune them toa level which is just appropriate for the life spanpotential of a given species.

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  1. Alexander Bürkle

    Present address: Department of Gerontology, University of Newcastle,IHE, Wolfson Research Centre, Newcastle General Hospital, WestgateRoad, Newcastle upon Tyne, NE4 6BE, UK

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  1. Abteilung Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    Alexander Bürkle

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Bürkle, A. Poly(ADP-ribosyl)ation: a posttranslational proteinmodification linked with genome protection andmammalian longevity. Biogerontology 1, 41–46 (2000). https://doi.org/10.1023/A:1010089924898

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