Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability.
Activation of poly(ADP-ribose) polymerase-1 (PARP-1) is an immediate cellular reaction to DNA strand breakage as induced by alkylating agents, ionizing radiation or oxidants. The resulting formation of protein-coupled poly(ADP-ribose) facilitates survival of proliferating cells under conditions of DNA damage, probably via its contribution to DNA base-excision repair. Furthermore, based on recent results there is a role emerging for PARP-1 as a negative regulator of genomic instability in cells under genotoxic stress. Regarding possible applications for clinical cancer therapy with DNA-damaging agents, it appears that both inhibition and up-regulation of the poly(ADP-ribosyl)ation response in the malignant cells to be eradicated are promising strategies to improve the outcome of such therapy, albeit for different reasons.
Bürkle
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Department of Gerontology, Institute for the Health of the Elderly, University of Newcastle upon Tyne, IHE, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, NE4 6BE, UK. Alexander.Buerkle@ncl.ac.uk
D000818:Animals; D002869:Chromosome Aberrations / Q000235:genetics*; D004249:DNA Damage; D004789:Enzyme Activation; D016678:Genome; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D011065:Poly(ADP-ribose) Polymerases