Poly(ADP-ribosyl)ation and aging

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2004
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Experimental Gerontology. Elsevier. 2004, 39(11-12), pp. 1599-1601. ISSN 0531-5565. eISSN 1873-6815. Available under: doi: 10.1016/j.exger.2004.07.010
Zusammenfassung

Poly(ADP-ribosyl)ation is a DNA strand break-driven post-translational modification of proteins catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), with NAD+ serving as substrate. Poly(ADP-ribosyl)ation is triggered by DNA strand breaks, is functionally associated with DNA repair pathways and is a survival factor for cells under low to moderate levels of genotoxic stress. We have previously described a positive correlation between poly(ADP-ribosyl)ation capacity of mononuclear blood cells with longevity of mammalian species. Our comparison of purified recombinant human and rat PARP-1 revealed that this correlation might be explained in part by evolutionary sequence divergence. We have also developed molecular genetic approaches to modulate the poly(ADP-ribosyl)ation status in living cells. Our results revealed that PARP-1 acts as a negative regulator of DNA damage-induced genomic instability, the latter being known as an important driving force for carcinogenesis. Our recent data obtained in transgenic mice with selective expression of a dominant negative version of PARP-1 in basal skin keratinocytes indicate that PARP-1 activity suppresses skin papilloma formation in a two-stage skin carcinogenesis protocol. It is tempting to speculate that increased poly(ADP-ribosyl)ation capacity in long-lived species might help retard the accumulation of DNA damage and of mutations and thus slow down the rate of aging and of carcinogenesis more efficiently as compared with short-lived animals.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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Aging, PARP-1, DNA base-excision repair, Genomic instability, Cancer
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ISO 690BÜRKLE, Alexander, Sascha BENEKE, Marie-Laure MUIRAS, 2004. Poly(ADP-ribosyl)ation and aging. In: Experimental Gerontology. Elsevier. 2004, 39(11-12), pp. 1599-1601. ISSN 0531-5565. eISSN 1873-6815. Available under: doi: 10.1016/j.exger.2004.07.010
BibTex
@article{Burkle2004PolyA-52111,
  year={2004},
  doi={10.1016/j.exger.2004.07.010},
  title={Poly(ADP-ribosyl)ation and aging},
  number={11-12},
  volume={39},
  issn={0531-5565},
  journal={Experimental Gerontology},
  pages={1599--1601},
  author={Bürkle, Alexander and Beneke, Sascha and Muiras, Marie-Laure}
}
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