Abstract
The silent information regulator 2 (Sir2) family catalyzes NAD+‐dependent protein deacetylation and functions in the regulation of gene silencing, chromatin structure, and longevity. O‐acetyl‐ribose (OAADPr) is a unique product of the Sir2 reaction. In Saccharomyces cerevisiae, we discovered three activities that metabolize OAADPr, an esterase, an acetyl transferase, and a Nudix hydrolase, Ysa1. In vitro, Ysa1 possesses comparable activity towards ADP‐ribose (ADPr) and OAADPr. We compared ADPr/OAADPr metabolizing activities among the wild type, Ysa1 deletion, and Ysa1 over expression strains. These data suggest that Ysa1 is a major ADPr/OAADPr metabolizing enzyme in vivo. N‐acetyl–ADPr analogs were utilized to indicate that OAADPr is directly hydrolyzed by Ysa1, and not through a pathway that first involves conversion of OAADPr to ADPr by the esterase. Using a TAP‐Ysa1 strain and cell fractionation, we localized the TAP signal to mitochondria. We propose that Ysa1 controls ADPr/OAADPr levels and is important for maintaining mitochrondrial function during cellular stress. Research supported by NIH.
Published Version
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