Abstract
3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthesis, is toxic to cells which incorporate and repair 5-hydroxymethyl-2’-deoxyuridine (HmdUrd). To demonstrate that incorporation and repair of HmdUrd stimulates synthesis of poly(ADP-ribose) from intracellular NAD, V79 hamster cells were treated with HmdUrd and intracellular NAD levels were measured. HmdUrd is incorporated into DNA as a thymidine analogue resulting in extensive substitution of thymine residues with 5hydroxymethyluracil (HmUra) residues. These HmUra residues are then subject to excision by action of HmUra-DNA glycosylase. Following HmdUrd treatment, NAD levels fell markedly (80-90%) within four hours and remained low for at least 10 hours before partially recovering by 24 hours. The degree of NAD lowering was dose dependent and paralleled net HmdUrd incorporation. The NAD lowering was largely prevented by concurrent treatment with 4 mM 3AB. No effects on NAD levels were seen following treatment with dThd or Brdurd, indicating that the effects on NAD result from incorporation of a nucleoside which puts large amounts of a repairable modification into DNA. To confirm that both incorporation and repair are necessary for the effects of HmdUrd on intracellular NAD, mutant cell strains derived from V79 cells deficient in either the ability to incorporate or to repair HmdUrd were examined. HmdUrd did not produce NAD lowering in either mutant cell strain. These results demonstrate that poly(ADP-ribose) synthesis can result directly and exclusively from repair of DNA base modifications.
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© 1992 Springer Science+Business Media New York
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Boorstein, R.J., Haldar, J., Poirier, G., Putnam, D. (1992). DNA Base Excision Repair Stimulates Poly(ADP-Ribose) Synthesis. In: Poirier, G.G., Moreau, P. (eds) ADP-Ribosylation Reactions. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8718-1_29
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DOI: https://doi.org/10.1007/978-1-4419-8718-1_29
Publisher Name: Springer, New York, NY
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