|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 113, Issue 10 1727-1736, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
JM Raleigh and MJ O'Connell
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett Street, Melbourne VIC 8006, Australia.
The onset of mitosis is controlled by the cyclin dependent kinase Cdc2p. Cdc2p activity is controlled through the balance of phosphorylation and dephosphorylation of tyrosine-15 (Y15) by the Wee1p kinase and Cdc25p phosphatase. In the fission yeast Schizosaccharomyces pombe, detection of DNA damage in G(2) activates a checkpoint that prevents entry into mitosis through the maintenance of Y15 phosphorylation of Cdc2p, thus ensuring DNA repair precedes chromosome segregation. The protein kinase Chk1p is the endpoint of this checkpoint pathway. We have previously reported that overexpression of Chk1p causes a wee1(+)-dependent G(2) arrest, and this or irradiation leads to hyperphosphorylation of Wee1p. Moreover, Chk1p directly phosphorylates Wee1p in vitro. These data suggested that Wee1p is a key target of Chk1p action in checkpoint control. However, cells lacking wee1(+) are checkpoint proficient and sustained Chk1p overexpression arrests cell cycle progression independently of Wee1p. Therefore, up-regulation of Wee1p alone cannot enforce a checkpoint arrest. Chk1p can also phosphorylate Cdc25p in vitro. These phosphorylation events are thought to promote the interaction with 14-3-3 proteins the cytoplasmic retention of the 14-3-3/Cdc25p complexes. However, we show here that the G(2) DNA damage checkpoint is intact in cells that regulate mitotic entry independently of Cdc25p. Further, these cells are still sensitive to Chk1p-mediated arrest, and so down-regulation of Cdc25p is also insufficient to regulate checkpoint arrest. Conversely, inactivation of both wee1(+) and cdc25(+ )abolishes checkpoint control. We also show that activation of the G(2) DNA damage checkpoint induces a transient increase in Wee1p levels. We conclude that the G(2) DNA damage checkpoint simultaneously signals via both up-regulation of Wee1p and down-regulation of Cdc25p, thus providing a double-lock mechanism to ensure cell cycle arrest and genomic stability.
This article has been cited by other articles:
|
|
 |
|
  M. Ganzinelli, L. Carrassa, F. Crippa, M. Tavecchio, M. Broggini, and G. Damia Checkpoint Kinase 1 Down-Regulation by an Inducible Small Interfering RNA Expression System Sensitized In vivo Tumors to Treatment with 5-Fluorouracil Clin. Cancer Res., August 15, 2008; 14(16): 5131 - 5141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ahmed, B. Dul, X. Qiu, and N. C. Walworth Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe Genetics, November 1, 2007; 177(3): 1487 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kosoy, T. M. Calonge, E. A. Outwin, and M. J. O'Connell Fission Yeast Rnf4 Homologs Are Required for DNA Repair J. Biol. Chem., July 13, 2007; 282(28): 20388 - 20394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Sansam, J. L. Shepard, K. Lai, A. Ianari, P. S. Danielian, A. Amsterdam, N. Hopkins, and J. A. Lees DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint Genes & Dev., November 15, 2006; 20(22): 3117 - 3129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Calonge and M. J. O'Connell Antagonism of Chk1 Signaling in the G2 DNA Damage Checkpoint by Dominant Alleles of Cdr1 Genetics, September 1, 2006; 174(1): 113 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nitani, K.-i. Nakamura, C. Nakagawa, H. Masukata, and T. Nakagawa Regulation of DNA Replication Machinery by Mrc1 in Fission Yeast Genetics, September 1, 2006; 174(1): 155 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Yang, T.-C. Hsia, H.-M. Kuo, P.-D. L. Chao, C.-C. Chou, Y.-H. Wei, and J.-G. Chung INHIBITION OF LUNG CANCER CELL GROWTH BY QUERCETIN GLUCURONIDES VIA G2/M ARREST AND INDUCTION OF APOPTOSIS Drug Metab. Dispos., February 1, 2006; 34(2): 296 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, Y. Guo, Y. Li, Y. Jiang, S. Chubb, A. Azuma, P. Huang, A. Matsuda, W. Hittelman, and W. Plunkett Molecular Basis for G2 Arrest Induced by 2'-C-Cyano-2'-Deoxy-1-{beta}-D-Arabino-Pentofuranosylcytosine and Consequences of Checkpoint Abrogation Cancer Res., August 1, 2005; 65(15): 6874 - 6881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zachos, M. D. Rainey, and D. A. F. Gillespie Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication Structures Mol. Cell. Biol., January 15, 2005; 25(2): 563 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Agapova, J. L. Volodina, P. M. Chumakov, and B. P. Kopnin Activation of Ras-Ral Pathway Attenuates p53-independent DNA Damage G2 Checkpoint J. Biol. Chem., August 27, 2004; 279(35): 36382 - 36389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Lu, H. Niida, and M. Nakanishi Human SAD1 Kinase Is Involved in UV-induced DNA Damage Checkpoint Function J. Biol. Chem., July 23, 2004; 279(30): 31164 - 31170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Latif, N. R. d. Elzen, and M. J. O'Connell DNA damage checkpoint maintenance through sustained Chk1 activity J. Cell Sci., July 15, 2004; 117(16): 3489 - 3498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ahmed, C. Palermo, S. Wan, and N. C. Walworth A Novel Protein with Similarities to Rb Binding Protein 2 Compensates for Loss of Chk1 Function and Affects Histone Modification in Fission Yeast Mol. Cell. Biol., May 1, 2004; 24(9): 3660 - 3669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Carmichael, P. Provost, K. Ekwall, and T. C. Hobman Ago1 and Dcr1, Two Core Components of the RNA Interference Pathway, Functionally Diverge from Rdp1 in Regulating Cell Cycle Events in Schizosaccharomyces pombe Mol. Biol. Cell, March 1, 2004; 15(3): 1425 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Oltra, F. Verde, R. Werner, and G. D'Urso A novel RING-finger-like protein Ini1 is essential for cell cycle progression in fission yeast J. Cell Sci., February 22, 2004; 117(6): 967 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Harvey, D. M. Sheedy, A. R. Cuddihy, and M. J. O'Connell Coordination of DNA Damage Responses via the Smc5/Smc6 Complex Mol. Cell. Biol., January 15, 2004; 24(2): 662 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimada, T. Nakadai, and T.-a. Tamura TATA-Binding Protein-Like Protein (TLP/TRF2/TLF) Negatively Regulates Cell Cycle Progression and Is Required for the Stress-Mediated G2 Checkpoint Mol. Cell. Biol., June 15, 2003; 23(12): 4107 - 4120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. McMillan, C. L. Theesfeld, J. C. Harrison, E. S. G. Bardes, and D. J. Lew Determinants of Swe1p Degradation in Saccharomyces cerevisiae Mol. Biol. Cell, October 1, 2002; 13(10): 3560 - 3575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Synnes, E. A. Nilssen, E. Boye, and B. Grallert A novel chk1-dependent G1/M checkpoint in fission yeast J. Cell Sci., September 15, 2002; 115(18): 3609 - 3618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Price, Z. Jin, S. Rabinovitch, and S. D. Campbell Ectopic Expression of the Drosophila Cdk1 Inhibitory Kinases, Wee1 and Myt1, Interferes With the Second Mitotic Wave and Disrupts Pattern Formation During Eye Development Genetics, June 1, 2002; 161(2): 721 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Deming, C. A. Cistulli, H. Zhao, P. R. Graves, H. Piwnica-Worms, R. S. Paules, C. S. Downes, and W. K. Kaufmann The human decatenation checkpoint PNAS, September 26, 2001; (2001) 221430898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rhind and P. Russell Roles of the Mitotic Inhibitors Wee1 and Mik1 in the G2 DNA Damage and Replication Checkpoints Mol. Cell. Biol., March 1, 2001; 21(5): 1499 - 1508. [Abstract] [Full Text]
|
|
|
|
|
|
J. Lee, A. Kumagai, and W. G. Dunphy Positive Regulation of Wee1 by Chk1 and 14-3-3 Proteins Mol. Biol. Cell, March 1, 2001; 12(3): 551 - 563. [Abstract] [Full Text]
|
|
|
|
|
|
N Rhind and P Russell Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways J. Cell Sci., January 11, 2000; 113(22): 3889 - 3896. [Abstract] [PDF]
|
|
|
|
|
|
M. P. Gustafson, C. F. Thomas Jr., F. Rusnak, A. H. Limper, and E. B. Leof Differential Regulation of Growth and Checkpoint Control Mediated by a Cdc25 Mitotic Phosphatase from Pneumocystis carinii J. Biol. Chem., January 5, 2001; 276(1): 835 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Curman, B. Cinel, D. E. Williams, N. Rundle, W. D. Block, A. A. Goodarzi, J. R. Hutchins, P. R. Clarke, B.-B. Zhou, S. P. Lees-Miller, et al. Inhibition of the G2 DNA Damage Checkpoint and of Protein Kinases Chk1 and Chk2 by the Marine Sponge Alkaloid Debromohymenialdisine J. Biol. Chem., May 18, 2001; 276(21): 17914 - 17919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Deming, C. A. Cistulli, H. Zhao, P. R. Graves, H. Piwnica-Worms, R. S. Paules, C. S. Downes, and W. K. Kaufmann The human decatenation checkpoint PNAS, October 9, 2001; 98(21): 12044 - 12049. [Abstract] [Full Text] [PDF]
|
|
