Abstract
Maintenance of genomic integrity is essential to avoid cellular transformation, neoplasia, or cell death. DNA synthesis, mitosis, and cytokinesis are important cellular processes required for cell division and the maintenance of cellular homeostasis; they are governed by many extra- and intra-cellular stimuli. Progression of normal cell division depends on cyclin interaction with cyclin-dependent kinases (Cdk) and the degradation of cyclins before chromosomal segregation through ubiquitination. Multiple checkpoints exist and are conserved in the cell cycle in higher eukaryotes to ensure that if one fails, others will take care of genomic integrity and cell survival. Many genes act as either positive or negative regulators of checkpoint function through different kinase cascades, delaying cell cycle progression to repair the DNA lesions and breaks, and assuring equal segregation of chromosomes to daughter cells. Understanding the checkpoint pathways and genes involved in the cellular response to DNA damage and cell division events in normal and cancer cells, provides information about cancer predisposition, and suggests design of small molecules and other strategies for cancer therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Morgan, D. O. (1995) Principles of CDK regulation. Nature, 374, 131–134.
Morgan, D. O. (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell. Dev. Biol. 13, 261–291.
Morgan, D. O. (1999) Regulation of APC and the exit from mitosis. Nat. Cell. Biol. 2, E47–53
Pines, J. (1999) Four-dimensional control of the cell cycle. Nat. Cell. Biol. 1, E73–79.
Hartwell, L. H. and Weinert, T. A. (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629–634.
Weinert, T. A. and Hartwell, L. H. (1988) The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 246, 317–322.
McDonald III, E. R. and El-Deiry, W. S. (2001) Checkpoint genes in cancer. Ann. Med. 33, 113–122.
Nasmyth, K. (1996) Viewpoint: putting the cell cycle in order. Science 274, 1643–1645.
Pardee, A. B. (1989) G1 events and regulation of cell proliferation. Science 246, 603–608.
King, R. W., Jackson, P.A., and Kirschner, M. W. (1994) Mitosis in transition. Cell 79, 563–571.
King, R. W., Deshaies, R. J., Peters, J. M., and Kirshner, M. W. (1996) How proteolysis drives the cell cycle. Science 274, 1652–1659.
Shapiro, J. A. and Harper, J. W. (1999) Anticancer drug targets: cell cycle and checkpoint control. J. Clin. Invest. 104, 1645–1653.
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., and Weinberg, R. A. (1999) Creation of human tumor cells with defined genetic elements. Nature 400, 464–468.
Vogelstein, B. and Kinzler, K. W. (1993) The multistep nature of cancer. Trends in Genet. 9, 138–141.
Hayflick, L. and Moorhead, P. S. (1961) The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621.
Lingner, J., Hughes, T. R., Shevchenko, A., Mann, M., Lundblad, V., and Cech, T. R. (1997) Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276, 561–567.
Bodnar, A. G., Ouellette, M., Frolkis, M., et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352.
Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57–70.
Pearson, M., Carbone, R., Sebastiani, C., et al. (2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406, 207–210.
El-Deiry, W. S. (1998) Regulation of p53 downstream genes. Semin. Cancer Biol. 8, 345–357.
Ozoren, N. and El-Deiry, W. S. (2000) Introduction to cancer genes and growth control. In: DNA Alterations in Cancer Genetic and Epigenetic Changes (Ehrlich, M., ed.), Eaton Publishing, Natick, MA: pp. 3–43.
Hunter, T. (1997) Oncoprotein networks. Cell 88, 333–346.
Elledge, S. and Spottswood, M. (1991) A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1. EMBO J. 10, 2653–2659.
McDonald, E. R. 3rd and El-Deiry, W. S. (2000) Cell cycle control as a basis for cancer drug development (Review). Int. J. Onco. 16, 871–886.
Oehlen, L. J., Jeoung, D. I., and Cross, F. R. (1998) Cyclin-specific START events and the G1-phase specificity of arrest by mating factor in budding yeast. Mol. Gen. Genet. 258, 183–189.
Schwob, E. and Nasmyth, K. (1993) CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae. Genes Dev. 7, 1160–1175.
Fisher, D. L. and Nurse, P. (1996) A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. EMBO J. 15, 850–860.
Levine, K., Huang, K., and Cross, F. R. (1996) Saccharomyces cerevisiae G1 cyclins differ in their intrinsic functional specificities. Mol. Cell. Biol. 271, 25240–25246.
Tetsu, O. and McCormick, F. (2003) Proliferation of cancer cells despite Cdk2 inhibition. Cancer Cell 3, 233–245.
Baldin, V., Lukas, J., Marcote, M. J., Pgano, M., and Draetta, G. (1993) Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 7, 812–821.
Lukas, J., Bartkova, J., Rhode, M., Strauss, M., and Bartek, J. (1995) Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells, independently of Cdk4 activity. Mol. Cell. Biol. 15, 2600–2611.
Ohtsubo, M., Theodoras, A. M., Schumacher, J., Roberts, J. M., and Pagano, M. (1995) Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol. Cell. Biol. 15, 2612–2624.
Geng, Y., Whoriskey, W., Park, M., et al. (1999) Rescue of cyclin D1 deficiency by knockin cyclin E. Cell 97, 767–777.
Girard, F., Strausfeld, U., Fernandez, A., and Lamb, N. J. C. (1992) Cylcin A is required for the onset of DNA replication in mammalian fibroblast. Cell 67, 1169–1179.
Pagano, M., Pepperkok, F., Verde, F., Ansorge, W., and Draetta, G. (1992) Cyclin A is required at two points in the human cell cycle. EMBO J. 11, 961–971.
Geng, Y., Yu, Q., Sicinska, E., et al. (2003) Cyclin E ablation in the mouse. Cell 114, 431–443.
Roberts, J. M. and Sherr, C. J. (2003) Bared essentials of CDK2 and cyclin E. Nat. Genet. 35, 9–10.
Murphy, M., Stinnakre, M.-G., Senamaud-Beaufort, C., et al. (1997) Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nat. Genet. 15, 83–86.
Brandeis, M., Rosewell, I., Carrington, M., et al. (1998) Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero. Proc. Natl. Acad. Sci. USA 95, 4344–4349.
Kaffman, A., Herskowitz, I., Tjian, R., and O’Shea, E. K. (1994) Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85. Science 263, 1153–1156.
Schneider, K. R., Smith, R. L., and O’Shea, E. K. (1994) Phosphate-regulated inactivation of the kinase PHO80-PHO85 by the CDK inhibitor PHO81. Science 266, 122–126.
Lew J., Huang, Q. Q., Qi, Z., et al. (1994) A brain-specific activator of cyclin-dependent kinase 5. Nature 371, 423–426.
Tsai, L.-H., Delalle, I., Caviness, V. S., Chae, T., and Harlow, E. (1994) p53 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371, 419–423.
Morgan, D. O. and De Bondt, H. L. (1994) Protein kinase regulation: insights from crystal structure analysis. Curr. Opin. Cell Biol. 6, 239–246.
De Bondt, H. L., Rosenblatt, J., Jancarik, J., Jones, H. D., Morgan, D. O., and Kim, S. H. (1993) Crystal structure of cyclin-dependent kinase 2. Nature 363, 595–602.
Russo, A. A., Jeffrey, P. D., and Pavletich, N. P. (1996) Structural basis of Cdk activation by phosphorylation. Nat. Struct. Biol. 3, 696–700.
Fisher, R. P. and Morgan, D. O. (1994) A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase. Cell 78, 713–724.
Fesquet, D., Labbe, J. C., Derabcourt, J., et al. (1993) The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues. EMBO J. 12, 3111–3121.
Solomon, M. J., Harper, J. W., and Shuttleworth, J. (1993) CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15. EMBO J. 12, 3133–3142.
Matsuoka, M., Kato, J., Fisher, R. P., Morgan, D. O., and Sherr, C. J. (1994) Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase. Mole. Cell. Biol. 14, 7265–7275.
Solomon, M., Glotzer, M., Lee, T. H., Phillipe, M., and Kirschner, M. (1990) Cyclin activation of p34cdc2. Cell 63, 1013–1024.
Poon, R. Y. C. and Hunter T. (1995) Dephosphorylation of Cdk2 Thr160 by the cyclin-dependent kinase interacting phosphatase KAP in the absence of cyclin. Science 27, 90–93.
Parker, L. L. and Piwnica-Worms, H. (1992) Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 257, 1955–1957.
Coleman, T. R. and Dunphy, W. G. (1994) Cdc2 regulatory factors. Curr. Opin. Cell. Biol. 6, 877–882.
Chang, F. and Herskowitz, I. (1990) Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of an G1 cyclin, CLN2. Cell 63, 999–1011.
Peter, M., Gartner, A., Horecka, J., Ammerer, G., and Herskowitz, I. (1993) FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Cell 73, 747–760.
Valtz, N., Peter, M., and Herskowitz, I. (1995) FAR1 is required for oriented polarization of yeast cells in response to mating pheromones. J. Cell. Biol. 131, 863–873.
Mendenhall, M. D. (1993) An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae. Science 259, 216–219.
Nugroho, T. T. and Mendenhall, M. D. (1994) An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells. Mole. Cell. Biol. 14, 3320–3328.
Donovan, J. D., Toyn, J. H., Johnson, A. L., and Johnson, L. H., (1994) P40SDB25, a putative CDK inhibitor, has a role in the M/G1 transition in Saccharomyces cerevisiae. Genes Dev. 8, 1640–1653.
Schneider, K. R., Smith, R. L., and O’Shea, E. K. (1994) Phosphate-regulated inactivation of the kinase PHO80-PHO85 by the CDK inhibitor PHO81. Science 266, 122–126.
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., and Elledge, S. J. (1993) The p21 Cdk interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75, 805–816.
El-Deiry, W. S., Tokino, T., Velcutescu, V. E., et al. (1993) Waf1, a potential mediator of p53 tumour suppression. Cell 75, 817–825.
Polyak, K., Lee, M. H., Erdjument-Bromage, H., et al. (1994) Cloning of p27kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extra-cellular antimitogenic signals. Cell 78, 59–66.
Toyoshima, H. and Hunter, T. (1994) p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78, 67–74.
Serrano, M., Hannon, G. J., and Beach, D. (1993) A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4. Nature 366, 704–707.
Hannon, G. J. and Beach, D. (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371, 257–261.
Cheng, M., Olivier, P., Diehl, J. A., et al. (1999) The p21Cip1nd p27Kip1 CDK “inhibitors” are essential activatrors of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 18, 1979–1990.
Luo, R. X., Postigo, A. A., and Dean, D. C. (1998) Rb interacts with histone deacetylase to repress transcription. Cell 92, 463–473.
Magnaghi-Jaulin, L., Groisman, R., Naguibneva, I., et al. (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391, 597–601.
Brehm, A., Miska, E. A., McCance, D. J., Reid, J. L., Bannister, A. J., and Kouzarides, T. (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391, 597–601.
Schulman, B. A., Lindstrom, D. L., and Harlow, E. (1998) Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. Proc. Natl. Acad. Sci. USA 95, 10453–10458.
Russo, A. A., Jeffery, P. D., Pattern, A. K., Massague, J., and Pavletich, N. P. (1995) Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 376, 313–320.
Roberts, J. M. (1999) Evolving ideas about cyclins. Cell 98, 129–132.
Sherr, C. J. (1993) Mammalian G1 cyclins. Cell 73, 1059–1065.
Kellogg, D. R., Mortiz, M., and Alberts, B. M. (1994) The centrosome and cellular organization. Annu. Rev. Biochem. 63, 639–674
Okuda, G., Horn, H. F., Tarapore, P., et al. (2000) Nucleophosmin/B23 is a target of Cdk2/cylin E in centrosome duplication. Cell 103, 127–140.
Fisk, H. A. and Winey, M. (2001) The mouse mps1p-like kinase regulates centrosome duplication. Cell 106, 95–104.
Stucke, V. M., Sillje, H. H. W., Arnaud, L., and Nigg, E. A. (2002) Human Mps1 kinase is required for the spindle assembly checkpoint but not for centrosome duplication. EMBO J. 21, 1723–1732.
Hinchcliffe, E. H., Miller, F. J., Cham, M., Khodjakov, A., and Sluder, G. (2001) Requirement of a centrosomal activity for cell cycle progression through G1 to S phase. Science 291, 1547–1550.
Piel, M., Nordberg, J., Euteneuer, U., and Bornens, M. (2001) Centrosome-dependent exit of cytokinesis in animal cells. Science 291, 1550–1553.
Doxsey, S. (2001) Re-evaluating centrosome function. Nature Rev. 2, 688–698.
Lane, H. A. and Nigg, E. A. (1996) Antibody microinjection reveals an essential role for human polo-like kinase (Plk1) in the functional maturation of mitotic centrosomes. J. Cell. Biol. 135, 1701–1713.
do Carno-Avides, M. and Glover, D. M. (1999) Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers. Science 283, 1733–1735.
Fry, A. M., Meraldi, P., and Nigg, E. A. (1998) A centrosomal function for the human Nek2 protein kinase, a member of the NIMA family of cell cycle regulators. EMBO J. 17, 470–481.
Helps, N. R., Luo, X., Barker, H. M., and Cohen, P. T. (2000) NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem. J. 349, 509–518.
Blangy, A., Lane, H. A., d’Herin, P., Harper, M., Kress, M., and Nigg, E. A. (1995) Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83, 1159–1169.
Giet, R., Uzbekov, R., Cubizolles, F., Le Guellec, K., and Prigent, C. (1999) The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XIEg5. JBC 272, 19418–19424.
Meraldi, P. and Nigg, E. A. (2002) The centrosome cycle. FEBS Lett. 521, 9–13.
Schumacher, J. M., Ashcroft, N., Donovan, P. J., and Golden, A. (1998) A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development 125, 4391–4402.
Nigg, E. A. (1995) Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays 17, 471–480.
Meraldi, P. and Nigg, E. A. (2002) The centrosome cycle, FEBS Lett. 521, 9–13.
Nigg, E. A. (2001) Mitotic kinases as regulators of cell division and its checkpoints. Nat. Rev. Mol. Cell. Biol. 2, 21–32.
Kramer, A., Neben, K., and Ho A. D. (2002) Centrosome replication, genomic instability and cancer. Leukemia 16, 767–775.
Tarapore, P., Horn, H. F., Tokuyama, Y., and Fukasawa, K. (2001) Direct regulation of the centrosome duplication cycle by the p53-p21 Waf1/cip1 pathway. Oncogene 20, 3173–3184.
Zhou, H., Kuang, J., Zhong, L., et al. (1998) Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat. Genet. 20, 189–193.
Koshland, D. and Strunnikov, A. (1996) Mitotic chromosome condensation. Annu. Rev. Cell Dev. Biol. 12, 305–333.
Cheung, P., Alis, D. C., and Sassone-Cors, P. (2000) Signaling to chromatin through histone modifications. Cell 103, 263–271.
Goto, H., Tomono, Y., Ajiro, K., et al. (1999) Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. JBC 274, 25543–25549.
Kimura, K., Hirano, M., Kobayashi, R., and Hirano, T. (1998) Phosphorylation and activation of 13S condensin by Cdc2 in vitro. Science 282, 487–490.
Evans, T., Rosenthal, E. T., Youngbloom, J., Distel, D., and Hunt, T. (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33, 389–396.
Thomas, G. (2000) An encore for ribosome biogenesis in the control of cell proliferation. Nat. Cell Biol. 2, E71–E72.
Schmelzle, T. and Hall, M. N. (2000) TOR, a central controller of cell growth. Cell 103, 253–262.
Rhode, J., Heitman, J., and Cardenas, M. E. (2001) The TOR kinases link nutrient sensing to cell growth. JBC 276, 9583–9586.
Fukunaga, R. and Hunter, T. (1997) MNK1, a new MAP kinase activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J. 16, 1921–1933.
Waskiewicz, A. J., Flynn, A., Proud, C. G., and Cooper, J. A. (1997) Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 16, 1909–1920.
Malumbres, M. and Pellicer, A. (1998) Ras pathways to cell cycle control and cell transformation. Front. Biosci. 3, D887–D912.
Ganoth, D., Bomstein, G., Ko, T. K., Larsen, B., Tyers, M., and Pagano, M. (2001) The cell-cycle regulatory protein Cks1 is required for SCF (Skp2)-mediated ubiquitinylation of p27. Nat. Cell Biol. 3, 321–324.
Webley, K., Bond, J. A., Jones, C. J., et al. (2000) Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Mol. Cell. Biol. 20, 2830–2838.
Baluchamy, S., Rjabi, H., Thimmapaya, R., Navaraj, A., and Thimmapaya, B. (2003) Repression of c-Myc and inhibition of G1 exit in cells conditionally overexpressing p300 that is not dependent on its histone acetyltransferase activity. Proc. Nat. Acad. Sci. USA 100, 9524–9529.
Lavita, P. and Jansen-Durr, P. (1999) E2F target genes and cell-cycle checkpoint control. Bioessays 21, 221–230.
Lundberg, A. S. and Weinberg, R. A. (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-CDK complexes. Mol. Cell. Biol. 18, 753–761.
Harbour, J. W., Luo, R. X., Dei Santi, A., Postigo, A. A., and Dean, D. C. (1999) Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98, 859–869.
Ezhevsky, S. A., Ho, A., Becker-Hapak, M., Davis, P. K., and Dowdy, S. F. (2001) Differential regulation of retinoblastoma tumor suppressor protein by G1 cyclin-dependent kinase complexes in vivo. Mol. Cell. Biol. 21, 4773–4784.
Sherr, C. J. and Roberts, J. M. (1999) Cdk inhibitors: positive and negative regulators of G1-phase progression. Genes and Dev. 13, 1501–1512.
Chan, H. M., Kristic-Demonacos, M., Smith, L., Demonacos, C., and La Thangue, N. B. (2001) Acetylation control of the retinoblastoma tumour-suppressor protein. Nat. Cell Bio. 3, 667–674.
Strohmaier, H., Spruck, C. H., Kaiser, P., Won, K. A., Sangfelt, O., and Reed S. I. (2001) Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 413, 316–322.
Koepp, D. M., Schaefer, L. K., Ye, X., Keyomarsi, K., Chu, C., and Harper, J. W. (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294, 173–177.
Welcker, M., Singer, J., Loeb, K. R., et al. (2003) Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol. Cell 12, 381–392.
Krek, W., Ewen, M. E., Shirodkar, S., Arany, Z., Kaelin, W. G., and Livingston, D. M. (1994) Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell 78, 161–172.
Krek, W., Xu, G., and Livingston, D. M. (1995) Cyclin A kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell 83, 1149–1158.
Dynlacht, B. D., Flores, O., Lees, J. A., and Harlow, E. (1994) Differential regulation of E2F transactivation by cyclin/cdk2 complexes. Genes Dev. 8, 1772–1786.
Nguyen, V. Q., Co, C., and Li, J. J. (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411, 1068–1073.
Yanow, S. K., Lygerou, Z., and Nurse, P. (2001) Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA replication. EMBO J. 20, 4648–4656.
Stillman, B. (1996) Cell cycle control of DNA replication. Science 274, 1659–1664.
Bell, S. P. and Dutta, A. (2002) DNA replication in eukaryotic cells. Ann. Rev. Biochem. 71, 333–374.
Delmolino, L. M., Saha, P., and Dutta, A. (2001) Multiple mechanisms regulate subcellular localization of human CDC6. JBC 276, 26947–26954.
Mendez, J. and Stillman, B. (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol. Cell. Biol. 20, 8602–8612.
Pelizon, C., Madine, M. A., Romanowski, P., and Lskey, R. A., (2000) Unphosphorylatable mutants of Cdc6 disrupt its nuclear export but still support DNA replication once per cell cycle. Genes Dev. 14, 2526–2533.
Nishitani, H., Taraviras, S., Lygerou, Z., and Nishimoto, T. (2001) The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. JBC 276, 44905–44911.
Walter, J. C. (2000) Evidence for sequential action of Cdc7 and Cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts. JBC 275, 39773–39778.
Walter, J. and Newport, J. (2000) Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase α. Mol. Cell 5, 617–627.
Wohlschlegel, J. A., Dwyer, B. T., Dhar, S. K., Cvetic, C., Walter, J. C., and Dutta, A. (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290, 2309–2312.
Yanagi, K. I., Mizuno, T., You, Z., and Hanaoka, F. (2002) Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. JBC 277, 40871–40880.
McGarry, T. J. (2002) Geminin deficiency causes a Chk1-dependent G2 arrest in Xenopus. Mol. Cell. Biol. 13, 3662–3671.
McGarry, T. J. and Kirschner, M. W. (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93, 1043–1053.
Yamaguchi, R. and Newport, J. (2003) A role for Ran-GTP and Crm1 in blocking re-replication. Cell 113, 115–125.
Lee, J., Kumagai, A., and Dunphy, W. G. (2003) Claspin, a Chk1 regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17. Mol. Cell. Biol. 11, 329–340.
Zhao, H., Watkins, J. L., and Piwnica-Worms, H. (2002) Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc. Nat. Acad. Sci. USA 99, 14795–14800.
Leone, G., Sears, R., Huang, E., et al. (2001) Myc requires distinct E2F activities to induce S phase and apoptosis. Mol. Cell 8, 105–113.
Waga, S., Hannon, G. J., Beach, D., and Stillman, B. (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369, 574–578.
Zhao, J., Dynlacht, B., Imai, T., Hori, T.-A., and Harlow, E. (1998) Expression of NPAT, a novel substrate of cyclin E-Cdk2, promotes S phase entry. Genes Dev. 12, 456–461.
Elledge, S. J. (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274, 1664–1672.
Mailand, N., Podtelejnikov, A.V., Groth, A., Mann, M., Bartek, J., and Lukas, J. (2002) Regulation of G2/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO J. 21, 5911–5920.
Dulic, V., Stein, G. H., Far, D. F., and Reed, S. J. (1998) Nuclear accumulation of p21 Cip1 at the onset of mitosis: a role at the G2/M phase transition. Mol. Cell. Biol. 18, 546–557.
Hu, B., Mitra, J., Heuvel, S.V.D., and Enders, G. H. (2001) S and G2 phase role for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells. Mol. Cell. Biol. 21, 2755–2766.
Clay-Farrace, L., Pelizon, C., Santamaria, D., Pines, J., and Laskey, R. A. (2003) Human replication protein Cdc6 prevents mitosis through a checkpoint mechanism that implicates Chk1. EMBO J. 22, 704–712.
Musacchio, A. and Kardwick, K. G. (2002) The spindle checkpoint: structural insights into dynamic signaling. Nat. Rev. Mol. Biol. 3, 731–741.
Russel, P. (1998) Checkpoints on the road to mitosis. Trends Biochem. Sci. 23, 399–402.
Qian, Y. W., Erikson, E., Li, C., and Maller, J. L. (1998) Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis. Mol. Cell. Biol. 18, 4262–4271.
Kumagai, A. and Dunphy, W. G. (1996) Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science 273, 1377–1380.
Scolnick, D. M. and Halazonetis, T. D. (2000) Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Nature 406, 430–435.
Mollinari, C., Reynaud, C., Martineau-Thuillier, S., et al. (2003) The mammalian passenger protein TD-60 is an RC1 family member with an essential role in prometaphase to metaphase progression. Dev. Cell 5, 295–307.
Cobbe, N. and Heck, M. M. (2000) SMCs in the world of chromosome biology—from prokaryotes to higher eukaryotes. J. Struct. Biol. 129, 123–143.
Hirano, T. (2002) The ABCs of SMC proteins: two armed ATPpases for chromosome condensation, cohesion and repair. Genes Dev. 16, 399–414.
Jessberger, R. (2001) The many functions of SMC proteins in chromosome dynamics. Nat. Rev. Mol. Cell. Biol. 3, 767–778.
Hagstrom, K. A. and Meyer, B. J. (2003) Condensin and cohesin: more then chromosome compactor and glue. Nat. Rev. Genet. 4, 520–534.
Gaucci, V., Koshland, D., and Strunnikov, A. (1997) A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91, 47–57.
Michalis, C., Ciosk, R., and Nasmyth, K. (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91, 35–45.
Waizenegger, I. C., Hauf, S., Meinke, A., and Peters, J. M. (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103, 399–410.
Nasmyth, K. (2002) Segregating sister genomes: the molecular biology of chromosome separation. Science 297, 559–565.
Peters, J. M. (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol. Cell 9, 931–943.
Hirano, T. and Mitchison, T. J. (1994) A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 79, 449–458.
Hirano, T., Kobayashi, R., and Hirano, M. (1997) Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein. Cell 89, 511–521.
Musacchio, A. and Hardwick, K. G. (2002) The spindle checkpoint: structural insights into dynamic signaling. Nat. Rev. Mol. Cell. Biol. 3, 731–741.
Hardwick, K. J. (1998) The spindle checkpoint. Trends Genet. 14, 1–4.
Hwang, L. H., Lau, L. F., Smith, D. L., et al. (1998) Budding yeast Cdc20: a target of the spindle checkpoint. Science 279, 1041–1044.
Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A., and Matsumoto, T. (1998) Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science 279, 1045–1047.
Maney, T., Ginkel, L. M., Hunter, A. W., and Wordeman, L. (2000) The kinetochores of higher eukaryotes: a molecular view. Int. Rev. Cytol. 194, 67–131.
Chan, G. K. T., Schaar, B. T., and Yen, T. J. (1998) Characteization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. J. Cell Biol. 143, 49–63.
Yao, X., Abrieu, A., Zheng, Y., Sullivan, K. F., and Cleveland, D. W. (2000) CENP-E forms a link between attachment of spindle microtubules and the mitotic checkpoint. Nat. Cell Biol. 2, 484–491.
Abrieu, A., Kahana, J. A., Wood, K.W., and Cleveland, D. W. (2000) CENP-E as an essential component of the mitotic checkpoint in vitro. Cell 102, 817–826.
Banks, J. D. and Heald, R. (2001) Chromosome movement: dynein-out at the kinetochore. Curr. Biol. 11, R128–R131.
Starr, D. A., Williams, B. C., Hays, T. S., and Goldberg, M. L. (1998) ZW10 helps recruit dynactin and dynein to the kinetochores. J. Cell Biol. 142, 763–774.
Chan, G. K., Jablonski, S. A., Starr, D. A., Goldberg, M. L., and Yen, T. J. (2000) Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores. Nat. Cell Biol. 2, 939–943.
Chen, R. H. (2002) BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1. J. Cell Biol. 158, 487–496.
Chen, R.-H., Waters, J. C., Salmon, E. D., and Murray, A. W. (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274, 242–246.
Chen, R. H., Shevchenko, A., Mann, M., and Murray, A. W. (1998) Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores. J. Cell Biol. 143, 283–295.
Chan, G. K., Schaar, B. T., and Yen, T. J. (1998) Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-E and hBUBR1. J. Cell Biol. 143, 49–63.
Taylor, S. S. and McKeon, F. (1997) Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 89, 727–735.
Taylor, S. S., Hussein, D., Wang, Y., Elderkin, S., and Morrow, C. J. (2001) Kinetochore localization and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells. J. Cell Sci. 114, 4385–4395.
Milliband, D. N. and Hardwick K. G. (2002) Fission yeast Mad3p is required for Mad2p to inhibit the anaphase-promoting complex and localizes to kinetochores in a Bub1p, Bub3p and Mph1p dependent manner. Mol. Cell. Biol. 22, 2728–2742.
Mao, Y., Abrieu, A., and Cleveland, D. W. (2003) Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell 114, 87–98.
Yu, H. G., Muszynski, M. G., and Dawe, R. K. (1999) The maize homologue of the cell cycle checkpoint protein MAD2 reveals kinetochore substructure and contrasting mitotic and meiotic localization patterns. J. Cell Biol. 145, 425–435.
Skoufias, D. A., Andreassen, P. R., Lacroix, F. B., Wilson, L., and Margolis, R. L. (2001) Mammalian Mad2 and Bub1/BubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints. Proc. Nat. Acad. Sci. USA 98, 4492–4497.
Zhou. J., Panda, D., Landen, J. W., Wilson, L., and Joshi, H. C. (2002) Minor alteration of microtubule dynamics causes loss of tension across kinetochore pairs and activates the spindle checkpoint. JBC 277, 17200–17208.
Kapoor, T. M., Mayer, T. U., Coughlin, M. L. and Mitchison, T. J. (2000) Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J. Cell Biol. 150, 975–988.
Adams, R. R., Carmena, M., and Earnshaw, W. E. (2001) Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol. 11, 49–54.
Tanaka, T. U., Rachidi, N., Janke, C., et al. (2002) Evidence that the Ipl1-Sli15 (aurora-kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108, 317–329.
Shimoda, S. L. and Solomon, F. (2002) Integrating functions at the kinetochores. Cell 109, 9–12.
Biggins, S. and Murray, A. W. (2001) The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev. 15, 3118–3129.
Murata-Hori, M. and Wang, Y. (2002) The kinase activity of aurora B is required for kinetochore-microtubule interactions in mitosis. Curr. Biol. 12, 894–899.
Howell, B. J., Hoffman, D. B., Fang, G., Murray, A. W., and Salmon, E. D. (2000) Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells. J. Cell Biol. 150, 1233–1250.
Howell, B. J., Farrar, E., Fang, G., and Salmon, E. D. (2001) Visualization of Cdc20 and BubR1 dynamics in living cells. Mol. Cell. Biol. 12(s), 315a.
Sharp-Baker, H. and Chen, R. H. (2001) Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. J. Cell Biol. 153, 1239–1250.
Abrieu, A., Magnaghi-Jaulin, L., Kahana, J. A., et al. (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106, 83–93.
Sudakin, V., Chan, G. K., and Yen, T. J. (2001) Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and Mad2. J. Cell Biol. 154, 925–936.
Basto, R., Gomes, R., and Karess, R. E. (2000) Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila. Nat. Cell Biol. 2, 939–943.
Luo, X., Tang, Z., Rizo, J., and Yu, H. (2002) The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Mol. Cell. Biol. 9, 59–71.
Sironi, L., Mapelli, M., Knapp, S., De Antoni, A., Jeang, K. T., and Musacchio, A. (2002) Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a “safety belt” binding mechanism for the spindle checkpoint. EMBO J. 21, 2496–2506.
Sironi, L., Melixetian, M., Faretta, M., Prosperini, E., Helin, K., and Musacchio, A. (2001) Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint. EMBO J. 20, 6371–6382.
Tang, G., Bharadwaj, R., Li, B., and Yu, H. (2001) Mad2-independent inhibition of APC-Cdc20 by the mitotic checkpoint protein BubR1. Dev. Cell 1, 227–237.
Brady, D. M. and Hardwick, K. G. (2000) Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function. Curr. Biol. 10, 675–678.
Pines, J. (2002) Cell cycle trials in Salamanca: workshop on G2/M progression and associated checkpoints. EMBO Rep. 3, 17–21.
Seeley, T. W., Wang, L., and Zhen, J. Y. (1999) Phosphorylation of human MAD1 by the BUB1 kinase in vitro. Biochem. Biophys. Res. Commun. 257, 589–595.
Hardwick, K. G., Weiss, E., Luca, F. C., Winey, M., and Murray, A. W. (1996) Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science 273, 953–956.
Michel, L. S., Liberal, V., Chatterjee, A., et al. (2001) MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409, 355–359.
Yao, X., Abrieu, A., Zheng, Y., Sullivan, K. F., and Cleveland, D. W. (2000) CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat. Cell Biol. 2, 484–491.
Fang, G. (2002) Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex. Mol. Cell. Biol. 13, 755–766.
Hoyt, M. A. (2000) Exit from mitosis: spindle pole power. Cell 102, 267–270.
Visintin, R., Craig, K., Hwang, E. S., Prinz, S., Tyers, M., and Amon, A. (1998) The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Cell 2, 709–718.
Jaspersen, S. L., Charles, J. F., Tinker-Kulberg, R. L., and Morgan, D. O. (1998) A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol. Cell. Biol. 9, 2803–2817.
Lee, S. E., Frenz, L. M., Wells, N. J., Johnson, A. L., and Johnston, L. H. (2001) Order of function of the budding-yeast mitotic exit-network proteins Tem1, Cdc15, Mob1, Dbf2, and Cdc5. Curr. Biol. 11, 784–788.
Bardin, A. J. and Amon, A. (2001) MEN and SIN: what’s the difference? Nat. Rev. Mol. Cell. Biol. 2, 815–823.
Shou, W., Seol, J. H., Shevchenko, A. et al. (1999) Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97, 233–244.
Stegmeier, F., Visintin, R., and Amon, A. (2002) Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell 108, 207–220.
Jensen, S., Geymonat, M., and Johnston, L. H. (2002) Mitotic exit: delaying the end without FEAR. Curr. Biol. 12, R221–R223.
Abrieu, A., Kahana, J. A., Wood, K. W., and Cleveland, D. W. (2000) CENP-E as an essential component of the mitotic checkpoint in vitro. Cell 102, 817–826.
Kalab, P., Weis, K., and Heald, R. (2002) Visualization of Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456.
Manser, E. (2002) Small GTPases take the stage. Development 3, 323–328.
Walczak, C. E., Vernos, I., Mitchison, T. J., Karsenti, E., and Heald, R. (1998) Model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. Curr. Biol. 8, 903.
Walczak, C. E. (2001) Ran hits the ground running. Nat. Cell. Biol. 3, E159–E161.
Sholey, J. M., Brust-Mascher, I., and Mogilner, A. (2003) Cell division. Nature 422, 746–752.
Ohba, T., Nakamura, M., Nishitani, H., and Nishimoto, T. (1999) Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science 284, 1356–1358.
Gruss, O. J., Carazo-Salas, R. E., Schatz, C. A., Guarguaglini, G., Kast, J., Wilm, M., et al. (2001) Ran induces spindle assembly by reversing the inhibitory effect of importin α on TPX2 activity. Cell 104, 83–93.
Terada, Y., Tatsuka, M., Suzuki, F., Yasuda, Y., Fujita, S., and Ostu, M. (1998) AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 17, 667–676.
Hall, A. (1998) Rho GTPases and the actin cytoskeleton. Science 279, 509–514.
Drechsel, D. N., Hyman, A. A., Hall, A., and Glotzer, M. (1997) A requirement for Rho and Cdc42 during cytokinesis in Xenopus embryos. Curr. Biol. 7, 12–23.
Takaishi, K., Sasaki, T., Kato, M., et al. (1994) Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility. Oncogene 9, 273–279.
Tatsumoto, T., Xie, X., Blumenthal, R., Okamoto, I., and Miki, T. (1999) Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis. J. Cell Biol. 147, 921–928.
Hirose, K., Kawashima, T., Iwamoto, I., Nosaka, T., and Kitamura, T. (2001) MagRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody. JBC 276, 5821–5828.
Minoshima, Y., Kawashima, T., Hirose, K., et al. (2003) Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev. Cell 4, 549–560.
Golsteyn, R. M., Mundt, K. E., Fry, A. M., and Nigg, E. A. (1995) Cell cycle regulation of the activity and subcellular localization of Plk1, a putative homolog of the mitotic spindle function. J. Cell Biol. 129, 1617–1628.
Abraham, R. T. (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 15, 2177–2196.
Bartek, J. and Lukas, J. (2001) Mammalian G1-and S-phase checkpoints in response to DNA damage. Curr. Opin. Cell Biol. 13, 738–747.
Melo, J. and Toczski, D. (2002) A unified view of the DNA-damage checkpoint. Curr. Opin. Cell Biol. 14, 237–245.
Shiloh, Y. (2003) ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 3, 155–168.
Zhou, B. B. S. and Elledge, S. J. (2000) The DNA damage response: putting checkpoints in perspective. Nature 408, 433–439.
McMahon, S. B., Wood, M. A., and Cole, M. D. (2000) The essential cofactor TRRAP recruits the histone acetylase hGCN5 to c-Myc. Mol. Cell. Biol. 20, 556–562.
Durocher, D. and Jackson, S. P. (2001) DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? Curr. Opin. Cell Biol. 13, 225–231.
Edwards, R. J., Bentley, N. J., and Carr, A. M. (1999) A Rad3-Rad26 complex responds to DNA damage independently of other checkpoint proteins. Nat. Cell Biol. 1, 393–398.
Cortez, D., Guntuku, S., Qin, J., and Elledge, S. J. (2001) ATR and ATRIP: parents in checkpoint signaling. Science 294, 1713–1716.
Wakayama, T., Kondo, T., Ando, S., Matsumoto, K., and Sugimoto, K. (2001) Pie1, a protein interacting with Mex1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 755–764.
Melo, J. A., Cohen, J., and Toczyski, D. P. (2001) Two checkpoint complexes are independently recruited to sites of DNA damage in vivo. Genes Dev. 15, 2809–2821.
Costanzo, V., Robertson, K., Ying, C. Y., et al. (2000) Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage. Mol. Cell 6, 649–659.
Smith, G. C., Cary, R. B., Lakin, N. D., et al. (1999) Purification of DNA binding properties of the ataxia-telangiectasia gene product ATM. Proc. Nat. Acad. Sci. USA 96, 11134–11139.
Andegeko, Y., Moyal, L., Mittelman, L., Tsarfaty, I., Shiloh, Y., and Rotman, G. (2001) Nuclear retention of ATM at sites of DNA double strand break. JBC 276, 38224–38230.
Bakkenist, C. J. and Kastan, M. B. (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 42, 499–506.
Petrini, J. H. (2000) The Mre11 complex and ATM: collaborating to navigate S phase checkpoint regulations. Genes Dev. 15, 2238–2249.
Lim, D. S., Kim, S. T., Xu, B., Maser, R. S., Lin, J., Petrini, J. H., et al. (2000) ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 404, 613–617.
Zhao, S., Weng, Y. C., Yuan, S. S., Lin, Y.T., Hsu, H.C., Lin, S. C., et al. (2000) Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Nature 405, 473–477.
D’Amours, D. and Jackson, S. P. (2001) The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes Dev. 15, 2238–2249.
Usui, T., Ogawa, H., and Petrini, J. H. (2001) A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7, 1255–1266.
Ritchie, K. B. and Petes, T. D. (2000) The Mre11p/Rad50p/Xrs2p complex and the Tel1p function in a single pathway for telomere maintenance in yeast. Genetics 155, 475–479.
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S. Y., et al. (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 16, 198–208.
Hammond, E. M., Denko, N. C., Dorie, M. J., Abraham, R. T., and Giaccia, A. J. Hypoxia links ATR and p53 through replication arrest. Mol. Cell. Biol. 22, 1834–1843.
Casper, A. M., Nghlem, P., Arlt, M. F., and Glover, T. W. (2002) ATR regulates fragile site stability. Cell 111, 779–789.
Bartek, J., Falck, J., and Lukas, J. (2001) CHK2 kinase—a busy messenger. Nat. Rev. Mol. Cell. Biol. 2, 877–886.
McGowan, C. H. (2002) Checking in on Cds1 (Chk2): a checkpoint kinase and tumor suppressor. Bioessays 24, 502–511.
Bartek, J. and Lukas, J. (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3, 421–429.
Gatei, M., Sloper, K., Sorensen, C. S., et al. (2003) Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. JBC 278, 14806–14811.
Sorensen, C. S., Syljuasen, R. G., Falck, J., et al. (2003) Chk1 regulates the Sphase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25C. Cancer Cell 3, 247–258.
Hirao, A., Kong, Y. Y., Matsuoka, S., et al. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287, 1824–1827.
Wang, B., Matsuoka, S., Carpenter, P. B., and Elledge, S. J. (2002) 53BP1, a mediator of the DNA damage checkpoint. Science 298, 1435–1438.
Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., and Qin, J. (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 14, 927–939.
Goldberg, M., Stucki, M., Falck, J., et al. (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421, 952–956.
Xie, S., Wu, H., Wang, Q., et al. (2002) Genotoxic stress-induced activation of Plk3 is partly mediated by Chk2. Cell Cycle 1, 424–429.
Yang, S., Kuo, C., Bisi, J. E., and Kim, M. K. (2002) PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat. Cell Biol. 4, 865–870.
Stevens, C., Smith, L., and LaThangue, N. B. (2003) Chk2 activates E2F-1 in response to DNA damage. Nat. Cell Biol. 5, 401–409.
Groth, A., Hansen, K., Nigg, E. A., Sillje, H. H. W., Lukas, J., and Bartek, J. (2003) Human Tousled like kinases are targeted by an ATM-and Chk1-dependent DNA damage checkpoint. EMBO J. 22, 1676–1687.
Lukas, C., Falck, J., Bartkova, J., Bartek, J., and Lukas, J. (2003) Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage. Nat. Cell Biol. 421, 952–960.
Liu, Q., Guntuku, S., Cui, X. S., et al. (2000) Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14, 1448–1459.
Takai, H., Tominaga, K., Motoyama, N., et al. (2000) Aberrant cell cycle checkpoint function and early embryonic death in chk1(-/-) mice. Genes Dev. 14, 1439–1447.
Takai, H., Naka, K., Okada, Y., et al. (2002) Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 21, 5159–5205.
Hirao, A., Cheung, A., Duncan, G., et al. (2002) Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)-dependent and an ATM-independent manner. Mol. Cell. Biol. 22, 6521–6532.
Zachos, G., Rainey, M. D., and Gillespie, D. A. (2003) Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. EMBO J. 22, 713–723.
Zhao, H., Watkins, J. L., and Piwnica-Worms, H. (2002) Disruption of the checkpoint kinase 1/ cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc. Natl. Acad. Sci. USA 99, 14795–14800.
Sorensen, C. S., Syljuasen, R. G., Falck, J., et al. (2003) Chk1 regulates the Sphase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell 3, 247–258.
Brown, G. W. and Kelly, T. J. (1999) Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase. Proc. Natl. Acad. Sci. USA 96, 8443–8448.
Santocanale, C. and Diffley, J. F. (1998) A Mec1-and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395, 615–618.
Lindsay, H. D., Griffiths, D. J., Edwards, R. J., et al. (1998) S-phase-specific activation of Cds1 kinase defines a sub-pathway of the checkpoint response in Schizosaccharomyces pombe. Genes Dev. 12, 382–395.
Venclovas, C. and Thelen, M. P. (2000) Structure based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes. Nucleic Acids Res. 28, 2481–2493.
Kostrub, C. F., Knudsen, K., Subramani, S., and Enoch, T. (1998) Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is phosphorylated in response to DNA damage. EMBO J. 17, 2055–2066.
Paciotti, V., Lucchini, G., Plevani, P., and Longhese, M. P. (1998) Mec1p is essential for phosphorylation of the yeast DNA damage checkpoint protein Ddc1p, which physically interacts with Mec3p. EMBO J. 17, 4199–4209.
Volkmer, E. and Karnitz, L. M. (1999) Human homologs of Schizosaccharomyces pombe Rad1, Hus1, and Rad9 form a DNA damage-responsive protein complex. JBC 274, 567–570.
Green, C. M., Erdjument-Bromage, H., Tempst, P., and Lownders, N. F. (2000) A novel Rad24 checkpoint protein complex closely related to replication factor C. Curr. Biol. 10, 39–42.
Bao, S., Tibbetts, R. S., Brumbaugh, K. M., et al. (2001) ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 411, 969–974.
Post, S., Weng, Y. C., Cimprich, K., Chen, L. B., Xu, Y., and Lee, E. Y. (2001) Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for the G1/S checkpoint activation in response to DNA damage. Proc. Natl. Acad. Sci. USA 98, 13102–13107.
Thelen, M. P., Venclovas, C., and Fidelis, K. (1999) A sliding clamp model for the Rad1 family of cell cycle checkpoint proteins. Cell 96, 769–770.
Roos-Mattjus, P., Vroman, B. T., Burtelow, M. A., Rauen, M., Eapen, A. K., and Karnitz, L. M. (2002) Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event. JBC 277, 43809–43812.
Burtelow, M. A., Kaufman, S. H., and Karnitz, L. M. (2000) Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage. JBC 275, 26343–26348.
Chen, M. J., Lin, Y. T., Lieberman, H. B., Chen, G., and Lee, E. Y. (2001) ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation. JBC 276, 16580–16586.
Melo, J. A., Cohen, J., and Toczyski, D. P. (2001) Two checkpoint complexes are independently recruited to sites of DNA damage in vivo. Genes Dev. 15, 2809–2821.
Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K., and Sugimoto, K. (2001) Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms. Science 294, 867–870.
Zou, L., Cortez, D. S. J., and Elledge, S. J. (2002) Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev. 16, 198–208.
Foiani, M., Lucchini, G., and Plevani, P. (1997) The DNA polymerase alpha-primase complex couples DNA replication, cell cycle progression and DNA-damage response. Trends Biochem. Sci. 22, 424–427.
Michael, W. M., Ott, R., Fanning, E., and Newport, J. (2000) Activation of the DNA replication checkpoint through RNA synthesis by primase. Science 289, 233–2137.
Rhind, N. and Russell, P. (2000) Checkpoints: it takes more then time to heal some wounds. Curr. Biol. 10, R908–911.
Cline, S. D. and Hanawalt, P. C. (2003) Who’s on first in the cellular response to DNA damage. Nat. Rev. Mol. Cell. Biol. 4, 361–372.
Caldecott, K. W. (2001) Mammalian DNA single-strand break repair: an X-ra(y)ted affair. Bioessays 23, 447–455.
Haber, J. E. (2000) Partners and pathways repairing a double-strand break. Trends Genet. 16, 259–264.
Memisoglu, A. and Samson, L. (2000) Base excision repair in yeast and mammals. Mut. Res. 451, 39–51.
deLaat, W. L., Jaspers, N. G., and Hoeijmakers, J. H. (1999) Molecular mechanism of nucleotide excision repair. Genes Dev. 13, 768–785.
Batty, D. P. and Wood, R. D. (2000) Damage recognition in nucleotide excision repair of DNA. Gene 241, 193–204.
Tang, J. Y., Hwang, B. J., Ford, J. M., Hanawalt, P. C., and Chu, G. (2000) Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Mol. Cell 5, 737–744.
Marra, G. and Schar, P. (1999) Recognition of DNA alterations by the mismatch repair system. Biochem. J. 338, 1–13.
Modrich, P. (1997) Strand-specific mismatch repair in mammalian cells. JBC 272, 24727–24730.
Viswanathan, M., Burdett, V., Baitinger, C., Mordrich, P., and Lovett, S. T. (2001) Redundant exonuclease involvement in Escherichia coli methyl-directed mismatch repair. JBC 276, 31053–31058.
Pegg, A. E. (2000) Repair of O6-alkylguanine by alkyltransferases. Mut. Res. 462, 83–100.
Aas, P. A., Otterlei, M., Falnes, P. O., Vagbo, C. B., Skorpen, F., Akbari, M., et al. (2003) Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421, 859–863.
Samson, L., Han, S., Marquis, J. C., and Rasmussen, L. J. (1997) Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair. Carcinogenesis 18, 919–924.
Sancar, G. B. (2000) Enzymatic photoreactivation: 50 years and counting. Mut. Res. 451, 25–37.
Tornaletti, S. and Hanawalt, P. C (1999) Effect of DNA lesions on transcription elongation. Biochimie 81, 139–146.
Conconni, A., Baspalov, V. A., and Smerdon, M. J. (2002) Transcription-coupled repair in RNA polymerase I-transcribed genes of yeast. Proc. Natl. Acad. Sci. USA 99, 649–654.
Dammann, R. and Pfeifer, G. P. (1997) Lack of gene-and strand-specific DNA repair in RNA polymerases III-transcribed human tRNA genes. Mol. Cell. Biol. 17, 219–229.
Wold, M. S. (1997) Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu. Rev. Biochem. 66, 61–92.
Evans, E., Moggs, J. G., Hwang, J. R., Egly, J. M., and Wood, R. D. (1997) Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. EMBO J. 16, 6559–6573.
Mu, D., Wakasugi, M., Hsu, D. S., and Sancar, A. (1997) Characterization of reaction intermediates of human excision repair nuclease. JBC 272, 28971–28979.
de Laat, W. L., Appeldoom, E., Sugasawa, K., Weterings, E., Jaspers, N. G., and Hoeijmakers, J. H. (1998) DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. Genes Dev. 12, 2598–2609.
Starita, L. M. and Parvin, J. D. (2003) The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair. Curr. Opin. Cell Biol. 15, 345–350.
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., and Bonner, W.M. (2000) A critical role of histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr. Biol. 10, 886–895.
Rogakou, E. P., Boon, C., Redon, C., and Bonner, W. M. (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J. Cell Biol. 146, 905–916.
Celeste, A., Peterson, S., Romanienko, P. J., et al. (2002) Genomic instability in mice lacking histone H2AX. Science 296, 922–927.
Redon, C., Pilch, D., Rogakou, E., Sedelnikova, O., Newrock, K., and Bonner, W. (2002) Histone H2A variants H2AX and H2AZ. Curr. Opin. Genet. Dev. 12, 162–169.
Gower, B. C., Avrutskaya, A. V., Latour, A. M., Koller, B. H., and Leadon, S. A. (1998) BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281, 1009–1012.
Moynahan, M. E., Chiu, J. W., Koller, B. H., and Jasin, M. (1999) Brca1 controls homology-directed DNA repair. Mol. Cell 4, 511–518.
Snouwaert, J. N., Gowen, L. C., Latour, A. M., et al. (1999) BRCA1 deficient embryonic stem cells display a decreased homologus recombination frequency and an increased frequency of non-homologous recombination that is corrected by expression of a brca1 transgene. Oncogene 18, 7900–7907.
Bartek, J., Bartkova, J., and Lukas, J. (1996) The retinoblastoma protein pathway and the restriction point. Curr. Opin. Cell Biol. 8, 805–814.
Coqueret, O. (2003) New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol. 13, 65–70.
Dotto, G. P. (2000) p21 (WAF1/Cip1): more than a break to the cell cycle. Biochim. Biophys. Acta 147, M43–56.
Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J., et al. (2000) Rapid destruction of Cdc25A in response to DNA damage. Science 288, 1425–1429.
Costanzo, V., Robertson, K., Ying, C. Y., et al. (2000) Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage. Mol. Cell 6, 649–659.
Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J., and Luka, J. (2001) The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410, 842–847.
Blasina, A., Price, B. D., Turenne, G. A., and McGowan, C. H. (1999) Caffeine inhibits the checkpoint kinase ATM. Curr. Biol. 9, 1135–1138.
Appella, E. and Anderson, C. W. (2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 268, 2764–2772.
Peiwen, F. and El-Deiry, W. S. (2003) p53 and radiation responses. Oncogene 22, 5774–5783.
Vogelstein, B., Lane, D., and Levine, A. J. (2000) Surfing the p53 network. Nature 408, 307–310.
Appella, E. and Anderson, C. W. (2000) Signaling to p53: breaking the post-translational modification code. Pathol. Biol. (Paris) 48. 227-245.
Gatti, A., Li, H.-H., Traugh, J. A., and Liu, X. (2000) Phosphorylation of human p53 on Thr-55. Biochemistry 39, 9837–9842.
Chehab, N. H., Malikzay, A., Appel, M., and Halazonetis, T. D. (2000) Chk2/hCds1 functions as a DNA damage checkpoint in G1 by stabilizing p53. Genes Dev. 14, 278–288.
Hirao, A., Kong, Y. Y., Matsuoka, S., et al. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287, 1824–1827.
Shieh, S. Y., Ahn, J., Tamai, K., Taya, Y., and Prives, C. (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14, 289–300.
Maya, R., Balass, M., Kim, S. T., et al. (2001) ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 15, 1067–1077.
Waterman, M. J., Stavridi, E. S., Waterman, J. L., and Halazonetis, T. D. (1998) ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat. Genet. 19, 175–178.
Venkitaraman, A. R. (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108, 171–182.
Cortez, D., Wang, Y., Qin, J., and Elledge, S. J. (1999) Requirement of ATM-dependent phosphorylation of BRCA1 in the DNA damage response to double-strand breaks. Science 286, 1162–1166.
Gatei, M., Zhou, B. B., Hobson, K., Scott, S., Young, D., and Khanna, K. K. (2001) Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies. JBC 276, 17276–17280.
El-Deiry, W. S. (2002) Transactivation of repair genes by BRCA1. Cancer Biol. Ther. 1, 490–491.
Xu, B., O’Donnell, A. H., Kim, S. T., and Kastan, M. B. (2002) Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing radiation. Cancer Res. 62, 4588–4591.
Lee, J. S., Collins, K. M., Brown, A. L., Lee, C. H., and Chung, J. H. (2000) hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404, 201–204.
Li, S., Ting, N. S., Zheng, L., et al. (2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406, 210–215.
Kim, S. T., Xu, B., and Kastan, M. B. (2002) Involvement of the cohesion protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev. 16, 560–570.
Yazdi, P. T., Wang, Y., Zhao, S., Patel, N., Lee, E. Y., and Qin, J. (2002) SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev. 16, 571–582.
Taniguchi, T., Garcia-Higuera, I., Xu, B., et al. (2002) Convergence of the Fanconi anemia and ataxia telangiectasia signaling pathways. Cell 109, 459–472.
Zeng, Y., Forbes, C. K., Wu, Z., Moreno, S., Piwnica-Worms, H., and Enoch, T. (1998) Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature 395, 507–510.
Hoffmann, I., Draetta, G., and Karsenti, E. (1994) Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J. 13, 4302–4310.
Xiao, Z, Chen, Z., Gunasekera, A. H., et al. (2003) Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. JBC 278, 21767–21773.
Karlsson, C., Katich, S., Hagting, A., Hoffman, I., and Pines, J. (1999) Cdc25B and Cdc25C differ markedly in their properties as initiators of mitosis. J. Cell Biol. 146, 573–584.
Peng, C.-Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S., and Piwnica-Worms, H. (1997) Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 277, 1501–1505.
Sanchez, Y. Wong, C., Thoma, R. S., et al. (1997) Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25C. Science 277, 1497–1501.
Lopez-Girona, A., Furnari, B., Mondesert, O., and Russell, P. (1999) Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature 397, 172–175
Furnari, B., Blasina, A., Boddy, M. N., McGowan, C. H., and Russell, P. (1999) Cdc25 inhibited in vivo and in vitro by checkpoint kinases cds1 and chk1. Mol. Cell Biol. 10, 833–845.
Weinert, T. A. (1997) DNA damage checkpoint meets the cell cycle engine. Science 277, 1450–1451.
Xu, B., Kim, S., and Kastan, M. B. (2001) Involvement of Brca1 in S-phase and G2-phase checkpoints after ionizing irradiation. Mol. Cell Biol. 21, 3445–3450.
Xu, X., Weaver, Z., Linke, S. P., et al. (1999) Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol. Cell 3, 389–395.
Cheng, I., Hunke, I., and Hardy, C. (1998) Cell cycle regulation of the Saccharomyces cerevisiae polo-like kinase Cdc5p. Mol. Cell Biol. 18, 7360–7370.
Sanchez, Y., Bachant, J., Wang, H., et al. (1999) Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms. Science 286, 1166–1171.
Qian, Y. W., Erikson, E., Li, C., and Maller, J. I. (1998) Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis. Mol. Cell Biol. 18, 4262–4271.
Smits, V. A., Klompmaker, R., Arnaud, L., Rijksen, G., Nigg, E. A., and Medema, R. H. (2000) Polo-like kinase-1 is a target of the DNA damage checkpoint. Nat. Cell Biol. 2, 672–676.
Malumbres, M. and Barbacid, M. (2001) To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer 1, 222–231.
Hall, M. and Peters, G. (1996) Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv. Cancer Res. 68, 67–108.
Loda, M., Cukor, B., Tam, S. W., et al. (1997) Increased proteosome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med. 3, 231–234.
Bell, D. W., Varley, J. M., Szydlo, T. E., et al. (1999) Heterozygous germ line hCHK2 mutations in Lifraumeni syndrome. Science 286, 2528–2531.
Jin, D. Y., Spencer, F., and Jeang, K. T. (1998) Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell 93, 81–91.
Zou, H., McGarry, T. J., Bernal, T., and Kirschner, M. W. (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285, 418–422.
Gemma, A., Seike, M., Seike, Y., et al. (2000) Somatic mutations of the hBUB1 mitotic checkpoint gene in primary lung cancer. Genes Chromo. Can. 29, 213–218.
Cahill, D. P., Lengauer, C., Yu, J., et al. (1998) Mutations of mitotic checkpoint genes in human cancer. Nature 392, 300–303.
Reis, R. M., Nakamura, M., Masuoka, J., et al. (2001) Mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in human bladder cancer, screening for mutations and loss of heterozygosity. Carcinogenesis 22, 813–815.
Wu, C., Kinrley, S. D., Xial, H., Chung, Y., Chung, D. C., and Zukerberg, L. R. (2001) Cables enhances Cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers. Cancer Res. 61, 7325–7332.
Corn, P. G., Summers, M. K., Fogt, F., et al. (2003) Frequent hypermethylation of the 5’ CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer. Carcinogenesis 24, 47–51.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Dash, B.C., El-Deiry, W.S. (2004). Cell Cycle Checkpoint Control Mechanisms That Can Be Disrupted in Cancer. In: Schönthal, A.H. (eds) Checkpoint Controls and Cancer. Methods in Molecular Biology™, vol 280. Humana Press. https://doi.org/10.1385/1-59259-788-2:099
Download citation
DOI: https://doi.org/10.1385/1-59259-788-2:099
Publisher Name: Humana Press
Print ISBN: 978-1-58829-214-8
Online ISBN: 978-1-59259-788-8
eBook Packages: Springer Protocols