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Poly(ADP-ribosyl)ation and aging

Lookup NU author(s): Professor Alexander Burkle, Dr Marie-Laure Muiras


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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. (C) 2004 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Burkle A, Beneke S, Muiras ML

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Experimental Gerontology: 7th International Symposium on the Neurobiology and Neuroendocrinology of Aging

Year of Conference: 2004

Pages: 1599-1601

ISSN: 0531-5565

Publisher: Elsevier Inc.


DOI: 10.1016/j.exger.2004.07.010

Library holdings: Search Newcastle University Library for this item

ISBN: 18736815