title: Control of dinucleoside polyphosphates by the FHIT-homologous HNT2 gene, adenine biosynthesis and heat shock in Saccharomyces cerevisiae.
abstract: BACKGROUND
  The FHIT gene is lost early in the development of many tumors. Fhit possesses intrinsic ApppA hydrolase activity though ApppA cleavage is not required for tumor suppression. Because a mutant form of Fhit that is functional in tumor suppression and defective in catalysis binds ApppA well, it was hypothesized that Fhit-substrate complexes are the active, signaling form of Fhit. Which substrates are most important for Fhit signaling remain unknown.
  
  
  RESULTS
  Here we demonstrate that dinucleoside polyphosphate levels increase 500-fold to hundreds of micromolar in strains devoid of the Saccharomyces cerevisiae homolog of Fhit, Hnt2. Accumulation of dinucleoside polyphosphates is reversed by re-expression of Hnt2 and is active site-dependent. Dinucleoside polyphosphate levels depend on an intact adenine biosynthetic pathway and time in liquid culture, and are induced by heat shock to greater than 0.1 millimolar even in Hnt2+ cells.
  
  
  CONCLUSIONS
  The data indicate that Hnt2 hydrolyzes both ApppN and AppppN in vivo and that, in heat-shocked, adenine prototrophic yeast strains, dinucleoside polyphosphates accumulate to levels in which they may saturate Hnt2.
authors.affiliation: Structural Biology & Bioinformatics Program, Kimmel Cancer Center, Philadelphia, Pennsylvania, USA. mrubiotx@mit.edu
authors.forename: Marta
authors.initials: M
authors.lastname: Rubio-Texeira
authors.forename: James M
authors.initials: JM
authors.lastname: Varnum
authors.forename: Pawel
authors.initials: P
authors.lastname: Bieganowski
authors.forename: Charles
authors.initials: C
authors.lastname: Brenner