Cuestiones y ejercicios propuestos

o En función de los conocimientos que poseemos sobre la regulación del ciclo celular en eucariotas, explica las siguientes observaciones experimentales:

• Cuando se inyecta MPF en células que acaban de salir de la fase S, se produce inmediatamente la condensación cromosómica y la vesiculación de la membrana nuclear, sin que se dé fase G2 (que normalmente dura varias horas).
• Cuando se introduce en las células una forma indestructible de ciclina, éstas entran en mitosis pero no pueden acabarla.
• En el experimento anterior ¿En qué momento queda detenida la mitosis?
• Mutaciones que inactivan la principal proteína fosfatasa provocan un largo retraso en la reconstrucción de la membrana nuclear

o ¿Qué tumores serán más sensibles al tratamiento con radioterapia, aquellos con el gen p53 salvaje o aquellos con un gen p53 mutado?

Animaciones multimedia

o Cell cycle control. CD-ROM de Lodish et al, 2000, Overview Animation 13-2. Resume los mecanismos de control en las diferentes fases del ciclo celular.
o Mitosis. CD-ROM de Lodish et al, 2000, Focus Animation 19-34. Detalla las características de las diferentes fases de la mitosis.
o Mitosis. CD-ROM de Alberts et al, 2002, Vídeo 18.2. Vídeo de microscopía de contraste interferencial que muestra las distintas fases de la mitosis y el característico comportamiento de los cromosomas en una célula de pulmón en cultivo.
o Nuclear envolope dynamics during mitosis. CD-ROM de Lodish et al, 2000, Vídeo 5.1. Vídeo de microscopía de fluorescencia que muestra el comportamiento de las láminas nucleares (marcadas mediante un anticuerpos fluorescentes) durante la mitosis.
o Meiosis. CD-ROM de Lodish et al, 2000, Focus Animation 8-2. Detalla los diferentes pasos de la meiosis.

Bibliografía complementaria - Libros

CONRAD, G.W. y SCHROEDER, T.E. eds. (1990) Cytokinesis: mechanisms of furrow formation during cell division. Ann. N.Y. Acad. Sci., Vol 582. New York: Academy of Sciences.
HYAMS, J.S. y BRINKLY, B.R. eds. (1989) Mitosis: Molecules and Mechanisms. Academic Press, San Diego, CA.
JOHN, P.C.L. (1981) The Cell Cycle. Cambridge University Press, Cambridge.
LLOYD, D., POOLE, R.K. y EDWARDS, S.W. (1982) The Cell Division Cycle. Academic Press, Nueva York.
MANDEL, L.J. y BENDS, D.L. (1986) The Role of Membranes in Cell Growth and Differentiation. Academic Press, Nueva York.
MOENS, P.B. ed. (1987) Meiosis. Academic Press, Nueva York.
MURRAY, A. y HUNT, T. (1994) The cell cycle. Oxford University Press, Oxford.
RAPPAPORT, R. (1996) Cytokinesis in Animal Cells. Cambridge University Press, Cambridge.
VARMUS, H. y WEINBERG, R.A. (1993) Genes and the biology of cancer. Scientific American Library, Nueva York.
ZIMMERMAN, A.M. y FORER, A. (1981) Mitosis/Cytokinesis. Academic Press, Nueva York.

Bibliografía complementaria - Artículos

ADAMS, P.D. y KAELIN, W.G. Jr. (1998) Negative control elements of the cell cycle in human tumors. Curr. Opin. Cell Biol. 10: 791-797.
BAILLY, E. y BORNENS, M. (1992) Centrosome and cell division. Nature 335: 300-301.
CANMAN, C.E. (2001) Replication checkpoint: preventing mitotic catastrophe. Curr. Biol. 11: R121-124.
CARPENTER, A.T. (1987) Gene conversion, recombination nodules, and the initiation of meiotic synapsis. Bioessay 6: 232-236.
CASPARI, T. (2000) How to activate p53. Curr. Biol. 10: R315-R317.
CAYIRLIOGLU, P. y DURONIO, R.J. (2001) Cell cycle: Flies teach an old dogma new tricks. Curr. Biol. 11: R178-181.
CHANDLEY, A.C. (1988) Meiosis in man. Trends Genet. 4: 79-84.
CRESPO, P. y LEON, J. (2000) Ras proteins in the control of the cell cycle and cell differentiation. Cell Mol. Life Sci. 57: 1613-1636.
CROSS, M. y DEXTER, T.M. (1991) Growth factors in development, transformation and tumorigenesis. Cell 64: 271-280.
DESALLE, L.M. y PAGANO, M. (2001) Regulation of the G1 to S transition by the ubiquitin pathway. FEBS Lett. 490: 179-189.
DONALDSON, A.D. y BLOW, J.J. (1999) The regulation of replication origin activation. Curr. Opin. Genet. Dev. 9: 62-68.
DUNPHY, W.G. (1994) The decision to enter mitosis. Trends Cell Biol. 4: 202-207.
DUNPHY, W.G. et al. (1988) The Xenopus Cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. Cell 54: 423-431.
EARNSHAW, W.C. y TOMKIEL, J.E. (1992) Centromere and kinetochore structure. Curr. Opin. Cell Biol. 4: 86-93.
ELLEDGE, S.J. (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274, 1664-1672.
FIELD, C. et al. (1999) Cytokinesis in eukariotes: a mechanistic comparison. Curr. Opin. Cell Biol. 11: 68-80.
FINGER, F.P. y WHITE, J.G. (2002) Fusion and fission: membrane trafficking in animal cytokinesis. Cell 108: 727-730.
FORSBURG, S.L. y NURSE, P. (1991) Cell cycle regulation in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. Annu. Rev. Cell Biol. 7: 227-256.
GAUTIER, J. et al. (1990) Cyclin is a component of maturation-promoting factor from Xenopus. Cell 60: 487-494.
GIACCIA, A.J. y KASTAN, M.B. (1998) The complexity of p53 modulation: emerging patterns from divergent signals. Genes & Devel. 12: 2973-2983.
HARBOUR, J.W. y DEAN, D.C. (2000) The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14: 2393-2409.
HARTWELL, L.H. et al. (1974) Genetic control of the cell division cycle in yeast. Science 183: 46-51. Una revision de los descubrimientos fundamentales que llevaron a L. Hartwell al premio Nobel.
HARTWELL, L.H. y WEINERT, T.A. (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246: 629-634.
HARTWELL, L.H. y KASTAN, M.B. (1994) Cell cycle control and cancer. Science 266: 1821-1828.
HIRANO, T. (2000) Chromosome cohesion, condensation, and separation. Annu. Rev. Biochem. 69: 115-144.
HULLEMAN, E y BOONSTRA, J. (2001) Regulation of G1 phase progression by growth factors and the extracellular matrix. Cell Mol. Life Sci. 58: 80-93.
JOHNSTON, G.C., PRINGLE, J.R. y HARTWELL, L.H. (1977) Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp. Cell Res. 105: 79-98.
KELLY, T.J. y BROWN, G.W. (2000) Regulation of chromosome replication. Annu. Rev. Biochem. 69: 829-880.
KING, R.W. et al. (1996) How proteolysis drives the cell cycle. Science 274: 1652-1659.
KIRSCHNER, M., NEWPORT, J. y GERHART, J. (1985) The timing of early developmental events in Xenopus. Trends Genet. 1: 41-47.
KLECKNER, N. (1996) Meiosis: how could it work? Proc. Natl. Acad. Sci. 93: 8167-8174.
KOSHLAND, D. y STRUNNIKOV, A. (1996) Mitotic chromosome condensation. Annu. Rev. Cell Dev. Biol. 12: 305-333.
LEVINE, A.J. (1997) p53, the cellular gatekeeper for growth and division. Cell 88: 323-331.
LOHKA, M.J., HAYES, M.K. Y MALLER, J.L. (1988) Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc. Natl. Acad. Sci. 85: 3009-3013.
MALUMBRES, M. y BARBACID, M. (2001) To cycle or not to cycle: a critical decision in cancer. Nature Rev. Cancer 1: 222-231.
MASSAGUÉ, J. y PANDIELLA, A. (1993) Membrane-anchored growth factors. Annu. Rev. Biochem. 62: 515-541.
MASUI, Y. y MARKERT, C.L. (1971) Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J. Exp. Zool. 177:129-145. Este trabajo demostró la existencia de un factor citoplasmático (cuya presencia era inducida por progesterona) que era capaz de inducir la reanudación de la meiosis en oocitos detenidos al final de la profase de la meiosis I. Este factor fue bautizado como MPF, de Factor Promotor de la Maduración, y posteriormente se encontró también en las células somáticas, donde induce el paso de la fase G2 a la Mitosis.
MORGAN, D. O. (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Devel. Biol. 13: 261-291.
MULLIGAN, G., y JACKS, T. (1998) The retinoblastoma gene family: cousins with overlapping interests. Trends Genet. 14: 223-229.
MURRAY, A.W. y KIRSCHNER, M.W. (1991) What controls the cell cycle? Sci. Am. 264: 56.
NASMYTH, K. (1996) Viewpoint: putting the cell cycle in order. Science 274:1643-1645.
NASMYTH, K., PETERS, J.M. y UHLMANN, F. (2000) Splitting the chromosome: cutting the ties that bind sister chromatids. Science 288: 1379-1385.
NEUFELD, T.P. y EDGAR, B.A. (1998) Connections between growth and the cell cycle. Curr. Opin. Cell Biol. 10: 784-790.
NURSE, P. (1975) Genetic control of cell size at cell division in yeast. Nature 256: 547-551.
NURSE, P. AND THURIAUX, P. (1980) Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics 96: 627-637.
OBAYA, A.J. y SEDIVY, J.M. (2002) Regulation of cyclin-Cdk activity in mammalian cells. Cell Mol. Life Sci. 59: 126-142.
PAULOVICH, A.G., TOCZYSKI, D.P. y HARTWELL L.H. (1997) When checkpoints fail. CeII 88: 315-321.
PIEL, M., NORDBERG, J., EUTENEUER, U., BORNENS, M. (2001) Centrosome-dependent exit of cytokinesis in animal cells. Science 291:1550-1553.
PLANAS-SILVA, M.D. y WEINBERG, R.A. (1997) The restriction point and control of cell proliferation. Curr. Opin. Cell Biol. 9: 768-772.
REED, S.I. (1997) Control of the G1/S transition. Cancer Surveys 29: 7-23.
ROOVERS, K y ASSOIAN, R.K. (2000) Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays 22: 818-826.
SHAH, J.V. y CLEVELAND, D.W. (2000) Waiting for anaphase: Mad2 and the spindle assembly checkpoint Cell 103: 997-1000.
SHERR, C.J. (1993) Mammalian G1 cyclins. Cell 73: 1059-1065.
SHERR, C.J. (1996) Cancer cell cycles. Science 274: 1672-1677.
SMITH, L.G. (2001) Plant cell division: building walls in the right places. Nat. Rev. Mol. Cell Biol. 2: 33.
SMITH, L.G. (2002) Plant cytokinesis: motoring to the finish. Curr. Biol. 12: R206-208.
STERN, B. y NURSE, P. (1996) A quantitative model for the Cdc2 control of S phase and mitosis in fission yeast. Trends Genet. 12: 345-350.
STILLMAN, B. (1996) Cell cycle control of DNA replication. Science 274: 1659-1664.
WEINBERG, R.A. (1995) The retinoblastoma protein and cell cycle control. Cell 85: 457-459.
WICK, S.M. (1991) Spatial aspects of cytokinesis in plant cells. Curr. Opin. Cell Biol. 3: 253-260.
ZAVITZ, K.H. y ZIPURSKY, S.L. (1997) Controlling cell proliferation in differentiating tissues: genetic analysis of negative regulators of G1 ? S-phase progression. Curr. Opin. Cell Biol. 9: 773-781.
ZEITLIN, S.G. y SULLIVAN, K.F. (2001) Animal cytokinesis: breaking up is hard to do. Curr. Biol. 11: R514-516.
ZHENG, L. y LEE, W.H. (2001) The retinoblastoma gene: a prototypic and multifunctional tumor suppressor. Exp Cell Res. 264: 2-18.
ZHOU, B.B. y ELLEDGE, S.J. (2000) The DNA damage response: putting checkpoints in perspective. Nature 408: 433-439.