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Comparative characterisation of poly(ADP-ribose) polymerase-1 from two mammalian species with different life span

Lookup NU author(s): Professor Alexander Burkle

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Abstract

DNA damage induced in higher eukaryotes by alkylating agents, oxidants or ionising radiation triggers the synthesis of protein-conjugated poly(ADP-ribose) catalysed by poly(ADP-ribose) polymerase-1 (PARP-1). Previously, cellular poly(ADP-ribosyl)ation capacity has been shown to correlate positively with the life span of mammalian species [Proc. Natl. Acad. Sci. USA 89 (1992) 11 759-11 763]. Here, we have tested whether this correlation results from differences in kinetic parameters of the enzymatic activity of PARP-1. We therefore compared recombinant enzymes, expressed in a baculovirus system, from rat and man as two mammalian species with extremely divergent life span. In standard activity assays performed in the presence of histones as poly(ADP-ribose) acceptors both enzymes showed saturation kinetics with [NAD+]. The kinetic parameters (k(cat), k(m) and k(cat)/k(m)) of the two enzymes were not significantly different. However, in assays assessing the auto-poly(ADP-ribosyl)ation reaction, both enzymes displayed second-order kinetics with respect to [PARP-1], and up to two-fold higher specific activity was observed for human versus rat PARP-1. We conclude that the correlation of poly(ADP-ribosyl)ation capacity with life span is not reflected in the kinetic parameters, but that subtle differences in primary structure of PARP-1 from mammalian species of different longevity may control the extent of the automodification reaction. Copyright (C) 2000 Elsevier Science Inc.

Publication metadata

Author(s): Beneke S, Alvarez-Gonzalez R, Bürkle A

Publication type: Article

Publication status: Published

Journal: Experimental Gerontology

Year: 2000

Volume: 35

Issue: 8

Pages: 989-1002

ISSN (print): 0531-5565

ISSN (electronic): 873-6815

Publisher: Elsevier B.V.

URL: http://dx.doi.org/10.1016/S0531-5565(00)00134-0

DOI: 10.1016/S0531-5565(00)00134-0

PubMed id: 11121685

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