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 i n vitro as a dinucleoside 5',5'''-P-1,P-3-triphosphate (Ap(3)A) hydrol ase. In this report, we show that the Saccharomyces cerevisiae APH1 ge ne product, which resembles human Fhit protein, also hydrolyzes dinucl eoside 5',5'-polyphosphates, with Ap(3)A being the preferred substrate . Accordingly, disruption of the APH1 gene produced viable S. cerevisi ae cells containing reduced Ap(3)A-hydrolyzing activity and a 30-fold- elevated Ap(3)N concentration.