Poly(ADP-ribose) polymerase (PARP): physiological and pathological roles
Makogon NV, Aleksieieva IM.
Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz58.03.095
Abstract
PARPs are a large family of 18 enzymes found in most eukaryotes. PARP-1, the most abundant isoform, is activated by DNA breaks and catalyzes the post-translational modifcation of proteins. It forms polymers of ADP-ribose and attaches them to acceptor proteins, including histones, DNA repair proteins, transcription factors. PARP-1 is a key enzyme involved in a maintenance of genomic stability. Excessive activation of the enzyme has been shown to contribute to tissue injury and infammatory disorders. PARP is a key mediator of cell death in oxidative stress, ischemia and DNA damage. It also promotes the activation of proinfammatory gene expression. Inhibition of PARP-1 provides signifcant protection in animal models of cardiovascular, autoimmune and infammatory diseases. PARP inhibitors have shown antitumor activity because they compromise ability of cancer cells to repair DNA. PARP-1 is a promising therapeutic target.
Keywords:
ПАРП, стабильность генома, гибельклеток, воспаление, ингибиторы ПАРП.
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