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Regulation of the cell cycle and apoptosis are two eukaryotic processes required to ensure maintenance of genomic integrity, especially in response to DNA damage. The ease with which yeast, amongst other eukaryotes, can switch from cellular proliferation to cell death may be the result of a common set of biochemical factors which play dual roles depending on the cell's physiological state. A wide variety of homologues are shared between different yeasts and metazoans and this conservation confirms their importance. This review gives an overview of key molecular players involved in yeast cell-cycle regulation, and those involved in mechanisms which are induced by cell-cycle dysregulation. One such mechanism is autophagy which, depending on the severity and type of DNA damage, may either contribute to the cell's survival or death. Cell-cycle dysregulation due to checkpoint deficiency leads to mitotic catastrophe which in turn leads to programmed cell death. Molecular players implicated in the yeast apoptotic pathway were shown to play important roles in the cell cycle. These include the metacaspase Yca1p, the caspase-like protein Esp1p, the cohesin subunit Mcd1p, as well as the inhibitor of apoptosis protein Bir1p. The roles of these molecular players are discussed.

Aspirin is a widely used anti-inflammatory and antithrombotic drug also known in recent years for its promising chemopreventive antineoplastic properties, thought to be mediated in part by its ability to induce apoptotic cell death. However, the full range of mechanisms underlying aspirin’s cancer-preventive properties is still elusive. In this study, we observed that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells, grown aerobically in ethanol medium. This occurred at both the gene level, as indicated by microarray and qRT-PCR analyses, and at the protein level as indicated by enzyme assays. These results show that in redox-compromised MnSOD-deficient yeast cells, but not in wild-type cells, aspirin starves the mitochondria of acetyl-CoA and likely causes energy failure linked to mitochondrial damage, resulting in cell death. Since acetyl-CoA is one of the least-studied targets of aspirin in terms of the latter’s propensity to prevent cancer, this work may provide further mechanistic insight into aspirin’s chemopreventive behavior with respect to early stage cancer cells, which tend to have downregulated MnSOD and are also redox-compromised.

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