Abstract
The recognition of cancer as a genetic disease has brought with it the observation that tumor development is the outcome of multiple independent mutational events occurring during somatic tissue growth (Peto et al. 1975; Fearon and Vogelstein 1990). These mutations in combination lead to abnormalities in growth control and genome instability in cancer cells. Advances in model organism studies have shown that these two attributes are frequently linked; that abnormalities in the control of cell cycle progression are often associated with increased errors in replicating and transmitting the parental genome to daughter cells. Because fundamental aspects of cell cycle control and chromosome distribution are clearly conserved in eukaryotic organisms, studies in model experimental systems are highly relevant to elucidation of the roles of these processes in tumor development in humans (Hartwell and Kastan 1994). This review will focus on recent advances in cell cycle control and genetic instability in the budding yeast Saccharomyces cerevisiae, with emphasis on experimental topics in which loss of cell cycle progression control decreases the fidelity of chromosome transmission to daughter cells. Viable single gene mutations that perturb both cell cycle control and genome stability in model organisms represent promising candidate tumor suppressor homologues. At this time, the connections between these functions in yeast and mammalian carcinogenesis are largely speculative, although the parallels are strong and warrant consideration.
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References
Allen J, Zhou Z, Siede W, Friedberg E, Elledge S (1994) The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev 8: 2416–2428
Amon A, Surana U, Muroff I, Nasmyth K (1992) Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae. Nature 355: 368–371
Ault J, Rieder C (1994) Centrosome and kinetochore movement during mitosis. Curr Biol 6: 41–49
Baker R, Massison D (1990) Isolation of the gene encoding the Saccharomyces cerevisiae centromere binding protein CP1. Mol Cell Biol 10: 2458–2467
Ballou C (1982) Yeast cell wall and cell surface. In: Strathern J, Jones E, Broach J (eds) The molecular biology of the yeast saccharomyces: metabolism and gene expression. Cold Spring Harbor, New York, pp 335–360
Bernat R, Borisy G, Rothfield N, Earnshaw WC (1990) Injection of anti-centromere antibodies in interphase disrupts events required for chromosome movement in mitosis. J Cell Biol 111: 1519–1533
Byers B (1981) Cytology of the yeast life cycle. In: Strathern J, Jones E, Broach J (eds) The molecular biology of the yeast saccharomyces: life cycle and inheritance. Cold Spring Harbor, New York, pp 59–96
Cai M, Davis R (1990) Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. Cell 61: 437–446
Campbell MS, Gorbsky GJ (1995) Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope antibody delays the onset of anaphase. J Cell Biol 129: 1195–1204
Carr A, Hoekstra M (1995) The cellular responses to DNA damage. Trends Cell Biol 5: 32–40
Coleman TR, Dunphy WG (1994) Cdc2 regulatory factors. Curr Opin Cell Biol 6: 877–882
Cross S, Sanchez D, Morgan C, Schimke M, Ramel S, Idzerda R, Raskind W, Reid B (1995) A p53-dependent mouse spindle checkpoint. Science 267: 1353–1356
Doheny K, Sorger P, Hyman A, Tugendriech S, Spencer F, Hieter P (1993) Identification of essential components of the S. cerevisiae kinetochore. Cell 73: 1–14
Earnshaw WC (1991) When is a centromere not a kinetochore? J Cell Sci 99: 1–4
Enoch T, Nurse P (1990) Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell 60: 665–673
Epstein C, Cross F (1992) CLB5: a novel B cyclin from budding yeast with a role in S phase. Genes Dev 6: 1695–1706
Fearon E, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767
Fitch I, Dahmann C, Surana U, Amon A, Nasmyth K, Goetsch L, Byers B, Futcher B (1992) Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae. Mol Biol Cell 3: 805–818
Ford J, al-Khodairy F, Fotou E, Sheldrick K, Griffiths D, Carr A (1994) 14-3-3 homologs required for the DNA damage checkpoint in fission yeast. Science 265: 533–535
Galaktionov K, Jessus C, Beach D (1995a) Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation. Genes Dev 9: 1046–1058
Galaktionov K, Lee A, Eckstein J, Draetta G, Meckler J, Loda M, Beach D (1995b) CDC25 phosphatases as potential human oncogenes. Science 269: 1575–1577
Goh P, Kilmartin J (1993) NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae. J Cell Biol 121: 503–512
Gorbsky G, Ricketts W (1993) Differential expression of a phosphoepitope at the kinetochores of moving chromosomes. J Cell Biol 122: 1311–1321
Greenwell P, Kronmal S, Porter S, Gassenhuber J, Obermaier B, Petes T (1995) TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82: 823–829
Guacci V, Hogan E, Koshland D (1994) Chromosome condensation and sister chromatid pairing in budding yeast. J Cell Biol 125: 517–530
Haarer B, Pringle J (1987) Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck. Mol Cell Biol 7: 3678–3687
Hari K, Santerre A, Sekelsky J, Mckim K, Boyd J, Hawley S (1995) The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell 82: 815–821
Hartwell L (1974) Saccharomyces cerevisiae cell cycle. Bacteriol Rev 38: 164–198
Hartwell L, Kastan M (1994) Cell cycle control and cancer. Science 266: 1821–1828
Hartwell L, Weinert T (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 240: 629–634
Hegemann JH, Fleig U (1993) The centromere of budding yeast. Bioessays 15: 451–460
Hegemann JH, Shero JH, Cottarel G, Philippsen P, Hieter P (1988) Mutational analysis of centromere DNA from chromosome VI of Saccharomyces cerevisiae. Mol Cell Biol 8: 2523–2535
Hoyt A, Totis L, Roberts T (1991) S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell 66: 507–517
Jehn B, Niedenthal R, Hegemann J (1991) In vivo analysis of the Saccharomyces cerevisiae centromere CDEIII sequence: requirements for mitotic chromosome segregation. Mol Cell Biol 11: 5212–5221
Jiang W, Lechner J, Carbon J (1993) Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore. J Cell Biol 121: 513–519
Kastan M, Zhan Q, El-Diery W, Carrier F, Jacks T, Walsh W, Plunkett B, Vogelstein B, Fornace J (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia telangiectasia. Cell 71: 587–597
Kilmartin J (1994) Genetic and biochemical approaches to spindle function and chromosome segregation in eukaryotic organisms. Curr Opin Cell Biol 6: 50–54
Kingsbury J and Koshland D (1993) Centromere function on minichromosomes from budding yeast. Mol Biol Cell 4: 859–870
Koshland D (1994) Mitosis: back to the basics. Cell 77: 951–954
Kung A, Sherwood S, Schimke R (1990) Cell line-specific differences in the control of cell cycle progression in the absence of mitosis. Proc Natl Acad Sci USA 87: 9553–9557
Lechner J, Carbon J (1991) A 240kD multisubunit protein complex, CBF3, is a major component of the budding yeast centromere. Cell 64: 717–725
Lew D, Reed S (1995) A cell cycle checkpoint monitors cell morphogenesis in budding yeast. J Cell Biol 129: 739–749
Li R, Murray A (1991) Feedback control of mitosis in budding yeast. Cell 66: 519–531
Li R, Havel C, Watson J, Murray A (1994) The mitotic feedback control gene MAD2 encodes the alpha subunit of a prenyltransferase: correction. Nature 371: 438
Li X, Nicklas RB (1995) Mitotic forces control a cell-cycle checkpoint. Nature 373: 630–632
Mellor J, Jiang W, Funk M, Rathjen J, Barnes C, Hiz T, Hegemann J, Philippsen P (1990) CPF1, a yeast protein which functions in centromeres and promoters. EMBO J 9: 4017–4026
Morrow D, Tagle D, Shiloh Y, Collins F, Hieter P (1995) TELI, an S. cerevisiae homolog of the gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1. Cell 82: 831–840
Murray A (1992) Creative blocks: cell-cycle checkpoints and feedback controls. Nature 359: 599–604
Murray A, Kirschner MW (1989) Dominoes and clocks: the union of two views of the cell cycle. Science 240: 614–621
Navas TA, Zhou Z, Elledge SJ (1995) DNA polymerase epsilon links the DNA replication machinery to the S phase checkpoint. Cell 80: 29–39
Newlon C (1988) Yeast chromosome replication and segregation. Microbiol Rev 52: 568–601
Nicklas B (1967) Chromosome micromanipulation: induced reorientation and the experimental control of segregation in meiosis. Chromosoma 21: 17–50
Nigg E (1993) Targets of cyclin-dependent protein kinases. Curr Biol 5: 187–193
Nurse P (1990) Universal control mechanism regulating onset of M phase. Nature 344: 503–508
Palmer R, Koval M, Koshland D (1989) The dynamics of chromosome movement in the budding yeast Saccharomyces cerevisiae. J Cell Biol 109: 3355–3366
Pangilinan F, Spencer F, (1996) Abnormal kinetochore structure activates the spindle assembly checkpoint in budding yeast. Mol Biol Cell
Panzeri L, Landonio L, Sotz A, Philippsen P (1985) Role of conserved sequence elements in yeast centromere DNA. EMBO J 4: 1867–1874
Paulovich A, Hartwell L (1995) A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 82: 841–847
Peter M, Herskowitz I (1994) Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell 79: 181–184
Peterson J, Ris H (1976) Electron microscopic study of the spindle and chromosome movement in the yeast Saccharomyces cerevisiae. J Cell Sci 22: 219–242
Peto R, Roe FJ, Lee PN, Levy L, Clack J (1975) Cancer and ageing in mice and men. Br J Cancer 32: 411–426
Piggott J, Rai R, Carter B (1982) A bifunctional gene product involved in two phases of the yeast cell cycle. Nature 298: 391–393
Pringle J, Hartwell L (1981) The Saccharomyces cerevisiae cell cycle. In: Strathern J, Jones E, Broach J (eds) The molecular biology of the yeast saccharomyces: life cycle and inheritance. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 97–142
Reed SI, Wittenburg C (1990) Mitotic role for the Cdc28 protein kinase of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 87: 5697–5701
Richardson H, Lew D, Henze M, Sugimoto K, Reed S (1992) Cyclin-B homologs in Saccharomyces cerevisiae function in S phase and in G2. Genes Dev 6: 2021–2034
Ridley A (1995) Rho-related proteins: actin cytoskeleton and cell cycle. Curr Opin Genet Dev 5: 24–30
Rieder C (1982) The formation, structure, and composition of the mammalian kinetochore fiber. Int Rev Cytol 79: 1–58
Rieder C, Palazzo R (1992) Colcemid and the mitotic cell cycle. J Cell Sci 102: 387–392
Rieder C, Schultz A, Cole R, Sluder G (1994) Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol 127: 1301–1310
Roberts T, Farr K, Hoyt A (1994) The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Mol Cell Biol 14: 8282–8291
Rothstein R (1991) Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol 194: 281–301
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle D, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali S, Simmons A, Clines G, Sartiel A, Gatti R, Chessa L, Sanai O, Lavin M, Jaspers N, Malcolm A, Taylor R, Arlett C, Miki T, Weissman S, Lovett M, Collins F, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268: 1749–1753
Schimke R, Kung A, Sherwood S, Sheridan J, Sharma R (1994) Life, death, and genomic change in perturbed cell cycles. Philos Trans R Soc Lond [B] 345: 311–317
Schwob E, Nasmyth K (1993) CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae. Genes Dev 7: 1160–1175
Seaton B, Yucel J, Sunnerhagen P, Subramani S (1992) Isolation and characterization of the Schizosaccharomyces pombe rad3 gene, involved in the DNA damage and DNA synthesis checkpoints. Gene 119: 83–89
Shiloh Y (1995) Ataxia-telangiectasia: closer to unravelling the mystery. Eur J Hum Genet 3: 116–138
Siede W, Friedberg AS, Friedberg EC (1993) RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 90: 7985–7989
Siede W, Friedberg AS, Dianova I, Friedberg EC (1994) Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents. Genetics 138: 271–281
Simerly C, Balczon R, Brmkley B, Schatten G (1990) Microinjeeted kinetochore antibodies interfere with chromosome movement in meiotic and mitotic mouse oocytes. J Cell Biol 111: 1491–1504
Smythe C, Newport J (1992) Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34CDC2. Cell 68: 787–797
Solomon M (1993) Activation of the various cyclin/cdc2 protein kinases. Curr Opin Cell Biol 5: 180–186
Sorger P, Murray A (1992) S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34CDC28. Nature 355: 365–368
Sorger P, Severin F, Hyman A (1994) Factors required for the binding of reassembled yeast kinetochores to microtubules in vitro. J Cell Biol 127: 995–1008
Spencer F, Hieter P (1992) Centromere DNA mutations induce a mitotic delay in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89: 8908–8912
Strunnikov A, Kingsbury J, Koshland D (1995) CEP3 encodes a centromere protein of Saccharomyces cerevisiae. J Cell Biol 128: 749–760
Stueland CS, Lew DJ, Cismowski MJ, Reed SI (1993) Full activation of p34CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae. Mol Cell Biol 13: 3744–3755
Sugino A (1995) Yeast DNA polymerases and their role at the replication fork. Trends Biochem Sci 20: 319–323
Tomkiel J, Cooke C, Saitoh H, Bernat R, Earnshaw W (1994) CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase. J Cell Biol 125: 531–545
Toyn J, Toone W, Morgan B, Johnston L (1995) The activation of DNA replication in yeast. Trends Biochem Sci 20: 70–73
Weinert T, Hartwell L (1988) The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241: 317–322
Weinert T, Hartwell L (1990) characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationaly in cell cycle arrest after DNA damage. Mol Cell Biol 10: 6554–6564
Weinert T, Hartwell L (1993) Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 134: 63–80
Weinert T, Kiser G, Hartwell L (1994) Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 8: 652–655
Yeh E, Skibbens R, Cheng J, Salmon E, Bloom K (1995) Spindle dynamics and cell cycle regulation of dynein in the budding yeast Saccharomyces cerevisiae. J Cell Biol 130: 687–700
Yen T, Compton D, Wise D, Zinkowski R, Brmkley B, Earnshaw W, Cleveland D (1991) CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase. EMBO J 10: 1245–1254
Zakian V, Runge K, Wang S (1990) How does the end begin? Formation and maintenance of telomeres in ciliates and yeast. Trends Genet 6: 12–16
Zheng P, Fay D, Burton J, Xiao H, Pinkham J, Stern D (1993) SPK1 is an essential S-phase specific gene of S. cerevisiae that encodes a serine/threonine/tyrosine kinase. Mol Cell Biol 13: 5829–5842
Zirkle R (1970) UV-microbeam irradiation of newt-cell cytoplasm: spindle destruction, false anapha se,and delay of true anaphase. Radiat Res 41: 516–537
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Spencer, F. (1997). Surveillance and Genome Stability in Budding Yeast: Implications for Mammalian Carcinogenesis. In: Kastan, M.B. (eds) Genetic Instability and Tumorigenesis. Current Topics in Microbiology and Immunology, vol 221. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60505-5_3
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