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Example sentences for: tfb
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In the case of the Hint-homologous HNT1 gene of S. cerevisiae , the phenotype of the single mutant was mild and the biological pathway, positive regulation of Kin28, the yeast homolog of Cdk7, was revealed by synthetic lethal interactions between hnt1 and hypomorphic alleles of cak1 , kin28 , ccl1 and tfb3 [ 9 ] . Because backup systems to limit problems with hnt2 mutant cells apparently exist, synthetic lethal interactions may be critical to identify the Hnt2 biological pathway.
Recently, discovery that the Hint-homologous HNT1 gene is required for high temperature growth on galactose and observations that alleles of cak1 , kin28 , ccl1 and tfb3 are hypersensitive to loss of Hnt1 enzyme activity provided evidence that Hnt1 enzyme activity positively regulates Kin28 function, particularly on galactose media [ 9 ] . Though phenotypic consequences of hnt2 mutations have yet to be discovered, our observations suggest that synthetic lethal interactions with hnt2 mutations are likely to be found in adenine prototrophic strains undergoing heat shock.
The human FHIT gene, located at the chromosome 3 fragile site FRA3B, is inactivated early in the development of many tumors [ 1 ] . Murine Fhit is also located at a fragile site [ 2 3 ] and mice heterozygous for disruption of Fhit , given low intragastric doses of the mutagen N-nitrosomethylbenzylamine, develop stomach and sebaceous tumors [ 4 ] that can be prevented by viral Fhit expression [ 5 ] . Fhit, a dimer of 147 amino acid subunits, is a member of the histidine triad (HIT) superfamily of nucleotide hydrolases and transferases [ 6 7 ] . Members of the Hint branch of the HIT superfamily are found in all forms of life [ 8 ] . The S. cerevisiae Hint homolog, Hnt1, and rabbit Hint possess adenosine monophosphoramidase activity that functions in yeast to positively regulate function of Kin28, Ccl1 and Tfb3, which constitute the kinase component of general transcription factor TFIIH [ 9 ] . A new Hint related protein, Aprataxin, is mutated in individuals with ataxia with oculomotor apraxia [ 10 11 ] and has a yeast homolog termed Hnt3 [ 9 ] . Members of the Fhit branch of the HIT superfamily have been found in fungi [ 12 13 ] , animals [ 2 14 15 ] and plants [ 7 ] and hydrolyze diadenosine tetraphosphate, diadenosine triphosphate and other 5'-5"'-dinucleoside polyphosphates.
Loss of Hnt1 enzymatic activity also renders cells hypersensitive to mutations in the cyclin H homolog Ccl1, the MAT1 homolog Tfb3, and to Cak1, the activating kinase for Kin28, all of which lead to destabilized Kin28 complexes and a likely increase in concentration of Kin28 monomers [ 30].
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