Chromosome stability and cellular senescence in yeast aging gene project

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1 : Aging mechanism by yeast HTR1 geneThe products of two genes, HTR1 and SGS1 are suggested to involve in the cellular aging process in yeast. We constructed a double mutant and found that two genes were epistatic. The fusion product of HTR1p with GFP was localized in the cytoplasm. The deletion of HTR1 gene conferred the ultra sensitivity to hydroxyurea, and this sensitive phenotype was rescued by one of the multi copy suppressor of htr1 mutant. Since this suppressor gene product was shown as a corepressor particularly for the genes in heterochromatin region associated with SIR complex, the senescence signal must be transmitted from HTR1 to SIR and finally to the genes in heterochromatin.2 : Function of SGS1 geneThe product of another aging gene SGS1 was shown to interact with DNA topoisomerases. To visualize the alteration of chromosome structure and the extent to cellular senescence, we marked various fragments of DNA topoisomerases with GFP. Among these fusion product, some showed strong affinity to nucleolus, rather than to chromosomes. The genetical meaning of this observation is yet to be investigated, but we got very interesting clue to understand nucleolus function in aging process in relation to DNA topoisomerases.