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Genetics. 2016 Oct;204(2):569-579. Epub 2016 Aug 15.

Nicotinamide Suppresses the DNA Damage Sensitivity of Saccharomyces cerevisiae Independently of Sirtuin Deacetylases.

Author information

1
Department of Cellular and Molecular Medicine, University of Ottawa, Ontario K1H 8M5, Canada Ottawa Institute of Systems Biology, University of Ottawa, Ontario K1H 8M5, Canada.
2
Department of Cellular and Molecular Medicine, University of Ottawa, Ontario K1H 8M5, Canada Ottawa Institute of Systems Biology, University of Ottawa, Ontario K1H 8M5, Canada mdowne2@uottawa.ca.

Abstract

Nicotinamide is both a reaction product and an inhibitor of the conserved sirtuin family of deacetylases, which have been implicated in a broad range of cellular functions in eukaryotes from yeast to humans. Phenotypes observed following treatment with nicotinamide are most often assumed to stem from inhibition of one or more of these enzymes. Here, we used this small molecule to inhibit multiple sirtuins at once during treatment with DNA damaging agents in the Saccharomyces cerevisiae model system. Since sirtuins have been previously implicated in the DNA damage response, we were surprised to observe that nicotinamide actually increased the survival of yeast cells exposed to the DNA damage agent MMS. Remarkably, we found that enhanced resistance to MMS in the presence of nicotinamide was independent of all five yeast sirtuins. Enhanced resistance was also independent of the nicotinamide salvage pathway, which uses nicotinamide as a substrate to generate NAD+, and of a DNA damage-induced increase in the salvage enzyme Pnc1 Our data suggest a novel and unexpected function for nicotinamide that has broad implications for its use in the study of sirtuin biology across model systems.

KEYWORDS:

DNA damage; NAD+; Pnc1; checkpoint; nicotinamide; sirtuins

PMID:
27527516
PMCID:
PMC5068847
DOI:
10.1534/genetics.116.193524
[Indexed for MEDLINE]
Free PMC Article

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