Poly(ADP-ribosyl)ation, genomic instability, and longevity.
Poly(ADP-ribosyl)ation is a DNA strandbreak-driven posttranslational modification of nuclear proteins that is catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), with NAD+ serving as substrate. Recently, additional PARP isoforms were described that seem to account for a minor fraction of cellular poly(ADP-ribose) synthesis. We have previously described a correlation between 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 do controls. At the functional level, recent data show that PARP-1 is a key regulator of alkylation-induced sister-chromatid exchange, imposing a negative control commensurate with the enzyme activity. PARP-1 activity may therefore be responsible for tuning the rate of genomic instability events that are provoked by the constant attack of endogenous and exogenous genotoxins to a level appropriate for the longevity potential of a given organism or species.
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Deutsches Krebsforschungszentrum, Abteilung Tumorvirologie, Heidelberg, Germany. Alexander.Buerkle@ncl.ac.uk
D000818:Animals; D002470:Cell Survival; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases