Words similar to dinucleoside
Example sentences for: dinucleoside
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An added benefit of these constructions is the availability of yeast strains that possess high levels of dinucleoside polyphosphates and at the same time express a mutant Fhit-homologous protein, because these are conditions which have been postulated to constitute the signaling form of Fhit [ 16 ] . Finally, using controlled genotypes we revisited conditions that lead to increased accumulation of dinucleoside polyphosphates [ 24 25 26 27 28 29 30 31 32 33 ] . Recognizing that hnt2 deletion is a pathological condition, we were particular interested in identifying conditions that lead to accumulation of such compounds in cells that contain a functional HNT2 gene, rather than simply identifying conditions that produce diadenosine polyphosphate accumulation in the absence of Hnt2.
Increases in dinucleoside polyphosphates in Hnt2+ cultures cannot be attributed to thermal inactivation of Hnt2 because the presence of HNT2 plasmids continues to reduce incremental increases in dinucleoside polyphosphates even in the fourth hour of the heat shock.
To survey dinucleoside polyphosphate induction as a function of potential stress conditions, strain BY71-6c was transformed with either pRS423 or pM1 (effectively hnt2Δ and hnt2Δ YEp KRS1 , respectively) and strain BY71-16d was transformed with the same plasmids (effectively HNT2Δ and HNT2Δ YEp KRS1 , respectively).
Here we discover a requirement of adenine biosynthesis for high-level dinucleoside polyphosphate accumulation in the absence of the Fhit homolog in S. cerevisiae . By constructing active site mutants of Hnt2 that were expressed in yeast, we demonstrate that ApppN and, to a lesser degree, AppppN levels are controlled by the Hnt2 active site.
Human Fhit [ 14 ] and the S. cerevisiae Fhit homolog [ 13 ] , which was called Aph1 but is here termed Hnt2 under nomenclature aproved by the Saccharomyces Genome Database, cleave ApppA more readily while Aph1, the S. pombe homolog, cleaves AppppA more readily [ 20 ] . Consistent with the ApppA hydrolase activity of purified Fhit protein, most cancer cell lines that are Fhit negative at the protein level have higher levels of ApppA than cell lines that are Fhit positive [ 21 ] . Nonetheless, the actual concentrations of dinucleoside polyphosphates were submicromolar in every cell culture sample [ 21 ] and thus, under the reported culture conditions, the measured dinucleoside polyphosphates would not be expected to occupy the Fhit active site substantially [ 19 ] . Dinucleoside polyphosphate levels were measured in adenine-requiring S. cerevisiae strains before or after disruption of the Fhit-homologous HNT2 gene [ 13 ] and in adenine-requiring S. pombe strains as a function of disruption and overexpression of the Fhit-homologous aph1 gene [ 22 ] . Recently, it was observed that diadenosine polyphosphates undergo a divalent cation-dependent conformational change that might mediate their biosynthesis, catabolism or signaling properties [ 23 ] .
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