Poly(ADP-ribosyl)ation, genomic instability, and longevity

Burkle, A

doi:10.1111/j.1749-6632.2000.tb06641.x

Poly(ADP-ribosyl)ation, genomic instability, and longevity

Lookup NU author(s): Professor Alexander Burkle

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Abstract

Poly(ADP-ribosyl)ation is a DNA strandbreak-driven posttranslational modification of nuclear proteins that is catalyzed by poly(ADP-ribose) polymerase-l (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.