How cells determine when to divide is critical for understanding virtually every biological process that cell proliferation is manifest. Abnormal patterns of cell division often cause disease, including cancer. Understanding cell division requires answers to each of two questions: How, and when do cells divide? Our goal is to answer the second question, since this process determines the overall rates of cell proliferation: once cells initiate their division, they are usually committed to complete it. Coordination between cellular metabolism and DNA replication determine when cells initiate division. Despite the fundamental significance of this coordination, the mechanisms that link metabolism with DNA replication in the nucleus remain largely unknown.
Using a model organism (baker's yeast), which is amenable to genetic and biochemical studies, our research aims to understand two aspects of this phenomenon: 1) how mitochondria, organelles that generate most of the cell's energy, actively promote initiation of DNA replication in the nucleus; and 2) how a stress signaling pathway called the unfolded protein response (UPR), acts as a homeostatic mechanism uniquely positioned to gauge overall metabolic activity before DNA replication. We hope that our research will impact the understanding of cell division mechanisms in a variety of fungal, plant, or animal systems, because these processes are conserved in all eukaryotic organisms, from yeast to humans.
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- Blank HM, Gajjar S, Belyanin A & Polymenis M (2009) Sulfur metabolism actively promotes initiation of cell division in yeast. PLoS One 4: e8018
- Blank HM, Li C, Mueller JE, Bogomolnaya LM, Bryk M & Polymenis M (2008) An increase in mitochondrial DNA promotes nuclear DNA replication in yeast. PLoS Genet 4: e1000047
- Pathak R, Blank HM, Guo J, Ellis S & Polymenis M (2007) The Dcr2p phosphatase destabilizes Sic1p in Saccharomyces cerevisiae. Biochem Biophys Res Commun 361: 700-4
- Guo J & Polymenis M (2006) Dcr2 targets Ire1 and downregulates the unfolded protein response in Saccharomyces cerevisiae. EMBO Rep 7: 1124-7
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- Blank HM, Totten JM & Polymenis M (2006) CDK control of membrane-bound organelle homeostasis. Cell Cycle 5: 486-8
- Pathak R, Bogomolnaya LM, Guo J & Polymenis M (2005) A role for KEM1 at the START of the cell cycle in Saccharomyces cerevisiae. Curr Genet 48: 300-9
- Han BK, Bogomolnaya LM, Totten JM, Blank HM, Dangott LJ & Polymenis M (2005) Bem1p, a scaffold signaling protein, mediates cyclin-dependent control of vacuolar homeostasis in Saccharomyces cerevisiae. Genes Dev 19: 2606-18
- Pathak R, Bogomolnaya LM, Guo J & Polymenis M (2004) Gid8p (Dcr1p) and Dcr2p function in a common pathway to promote START completion in Saccharomyces cerevisiae. Eukaryot Cell 3: 1627-38
- Bogomolnaya LM, Pathak R, Guo J, Cham R, Aramayo R & Polymenis M (2004) Hym1p affects cell cycle progression in Saccharomyces cerevisiae. Curr Genet 46: 183-92
- Guo J, Bryan BA & Polymenis M (2004) Nutrient-specific effects in the coordination of cell growth with cell division in continuous cultures of Saccharomyces cerevisiae. Arch Microbiol 182: 326-30
- Bryan BA, Knapp GS, Bowen LM & Polymenis M (2004) The UV response in Saccharomyces cerevisiae involves the mitogen-activated protein kinase Slt2p. Curr Microbiol 49: 32-4
- Bogomolnaya LM, Pathak R, Cham R, Guo J, Surovtseva YV, Jaeckel L & Polymenis M (2004) A new enrichment approach identifies genes that alter cell cycle progression in Saccharomyces cerevisiae. Curr Genet 45: 350-9
- Borkovich KA, Alex LA, Yarden O, Freitag M, Turner GE, Read ND, Seiler S, Bell-Pedersen D, Paietta J, Plesofsky N, Plamann M, Goodrich-Tanrikulu M, Schulte U, Mannhaupt G, Nargang FE, Radford A, Selitrennikoff C, Galagan JE, Dunlap JC, Loros JJ, Catcheside D, Inoue H, Aramayo R, Polymenis M, Selker EU, Sachs MS, Marzluf GA, Paulsen I, Davis R, Ebbole DJ, Zelter A, Kalkman ER, O'Rourke R, Bowring F, Yeadon J, Ishii C, Suzuki K, Sakai W & Pratt R (2004) Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol Mol Biol Rev 68: 1-108
- Bryan BA, McGrew E, Lu Y & Polymenis M (2004) Evidence for control of nitrogen metabolism by a START-dependent mechanism in Saccharomyces cerevisiae. Mol Genet Genomics 271: 72-81
- Han BK, Aramayo R & Polymenis M (2003) The G1 cyclin Cln3p controls vacuolar biogenesis in Saccharomyces cerevisiae. Genetics 165: 467-76
- Zettel MF, Garza LR, Cass AM, Myhre RA, Haizlip LA, Osadebe SN, Sudimack DW, Pathak R, Stone TL & Polymenis M (2003) The budding index of Saccharomyces cerevisiae deletion strains identifies genes important for cell cycle progression. FEMS Microbiol Lett 223: 253-8
- Wrobel C, Schmidt EV & Polymenis M (1999) CDC64 encodes cytoplasmic alanyl-tRNA synthetase, Ala1p, of Saccharomyces cerevisiae. J Bacteriol 181: 7618-20
- Polymenis M & Schmidt EV (1999) Coordination of cell growth with cell division. Curr Opin Genet Dev 9: 76-80
- Johnston KA, Polymenis M, Wang S, Branda J & Schmidt EV (1998) Novel regulatory factors interacting with the promoter of the gene encoding the mRNA cap binding protein (eIF4E) and their function in growth regulation. Mol Cell Biol 18: 5621-33
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