• Paike Jayadeva Bhat

      Articles written in Journal of Biosciences

    • Epigenetics of the yeast galactose genetic switch

      Paike Jayadeva Bhat Revathi S Iyer

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      The transcriptional activation of enzymes involved in galactose utilization (GAL genes) in Saccharomyces cerevisiae is regulated by a complex interplay between three regulatory proteins encoded by GAL4 (transcriptional activator), GAL3 (signal transducer) and GAL80 (repressor). The relative concentrations of the signal transducer and the repressor are maintained by autoregulation. Cells disabled for autoregulation exhibit phenotypes distinctly different from that of the wild type cells, enabling us to explore the biological significance of autoregulation. The redundancy in signal transduction due to the presence of GAL1 (alternate signal transducer) also makes it a suitable model to understand the phenomenon of epigenetics. In this article we review some of the recent attempts made to understand the importance of epigenetics in the establishment of cellular and transcriptional memory.

    • Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast


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      Tumour cells distinguish from normal cells by fermenting glucose to lactate in presence of sufficient oxygen and functionalmitochondria (Warburg effect). Crabtree effect was invoked to explain the biochemical basis of Warburg effect by suggestingthat excess glucose suppresses mitochondrial respiration. It is known that the Warburg effect and Crabtree effect aredisplayed by Saccharomyces cerevisiae, during growth on abundant glucose. Beyond this similarity, it was also demonstratedthat expression of human pro-apoptotic proteins in S. cerevisiae such as Bax and p53 caused apoptosis. Here, wedemonstrate that p53 expression in S. cerevisiae (Crabtree-positive yeast) causes increase in ROS levels and apoptosis whencells are growing on non-fermentable carbon sources but not on fermentable carbon sources, a feature similar to tumourcells. In contrast, in Kluyveromyces lactis (Crabtree-negative yeast) p53 causes increase in ROS levels and apoptosisregardless of the carbon source. Interestingly, the increased ROS levels and apoptosis are correlated to increased oxygenuptake in both S. cerevisiae and K. lactis. Based on these results, we suggest that at least in yeast, fermentation per se doesnot prevent the escape from apoptosis. Rather, the Crabtree effect plays a crucial role in determining whether the cellsshould undergo apoptosis or not.

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