Control of 5',5'-dinucleoside triphosphate catabolism by APH1, a Saccharomyces cerevisiae analog of human FHIT

The putative human tumor suppressor gene FHIT (fragile histidine triad) (M. Ohta et al., Cell 84:587-597, 1996) encodes a protein behaving in vitro as a dinucleoside 5',5"'-P1,P3-triphosphate (Ap3A) hydrolase. In this report, we show that the Saccharomyces cerevisiae APH1 gene product, which resembles human Fhit protein, also hydrolyzes dinucleoside 5',5'-polyphosphates, with Ap3A being the preferred substrate. Accordingly, disruption of the APH1 gene produced viable S. cerevisiae cells containing reduced Ap3A-hydrolyzing activity and a 30-fold-elevated Ap3N concentration.