Abstract
Poly(ADP-ribosyl)ation is a posttranslational protein modification catalyzed by poly(ADP-ribose) polymerase (PARP), a highly conserved nuclear enzyme which uses nicotinamide-adenine dinucleotide (NAD) as substrate (for review, see [1]). The DNA-binding domain of the enzyme specifically binds to DNA single-or double-strand breaks, resulting in enzyme activation. Thus, treatment of cells with chemical or physical carcinogens induces a dose-dependent stimulation of polymer synthesis and turnover. To understand the biological function(s) of poly(ADP-ribosyl)ation, NAD analogues have been extensively used as competitive inhibitors of poly(ADP-ribosyl)ation in intact cells. Such inhibitors (e.g.,benzamide and derivatives such as 3-aminobenzamide) have no influence on cell growth (at concentrations of 1 mM or lower) nor are they mutagenic or carcinogenic. They potentiate, however, cytotoxicity and chromosomal damage induced by carcinogen treatment, e.g., alkylating agents or ionizing radiation. These and other findings led to the view that poly(ADP-ribosyl)ation plays a role in DNA repair.
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Abbreviations
- 3AB :
-
3-aminobenzamide
- AF :
-
amplification factor
- DHFR :
-
dihydrofolate reductase
- EF :
-
enhancement factor
- MNNG :
-
N-methyl-N’-nitro-N-nitrosoguanidine
- MTX :
-
methotrexate
- PARP :
-
poly(ADP-ribose) polymerase
- PE :
-
plating efficiency
- SV40 :
-
Simian virus 40
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Bürkle, A., Grube, K., Küpper, JH. (1992). Poly(ADP-ribosyl)ation, Genetic Instability, and Aging. In: Zwilling, R., Balduini, C. (eds) Biology of Aging. Reihe der Villa Vigoni, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85789-8_14
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DOI: https://doi.org/10.1007/978-3-642-85789-8_14
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