cdc2 and the Regulation of Mitosis: Six Interacting mcs Genes

INVESTIGATIONS

cdc2 and the Regulation of Mitosis: Six Interacting mcs Genes

L. Molz, R. Booher, P. Young and D. Beach
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

A cdc2-3w weel-50 double mutant of fission yeast displays a temperature-sensitive lethal phenotype that is associated with gross abnormalities of chromosome segregation and has been termed mitotic catastrophe. In order to identify new genetic elements that might interact with the cdc2 protein kinase in the regulation of mitosis, we have isolated revertants of the lethal double mutant. The suppressor mutations define six mcs genes (mcs: mitotic catastrophe suppressor) that are not allelic to any of the following mitotic control genes: cdc2, wee1, cdc13, cdc25, suc1 or nim1. Each mcs mutation is recessive with respect to wild-type in its ability to suppress mitotic catastrophe. None confer a lethal phenotype as a single mutant but few of the mutants are expected to be nulls. A diverse range of genetic interactions between the mcs mutants and other mitotic regulators were uncovered, including the following examples. First, mcs2 cdc2w or mcs6 cdc2w double mutants display a cell cycle defect dependent on the specific wee allele of cdc2. Second, both mcs1 cdc25-22 or mcs4 cdc25-22 double mutants are nonconditionally lethal, even at a temperature normally permissive for cdc25-22. Finally, the characteristic suppression of the cdc25 phenotype by a loss-of-function wee1 mutation is reversed in a mcs3 mutant background. The mcs genes define new mitotic elements that might be activators or substrates of the cdc2 protein kinase.

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				K. M. Lee, I. Miklos, H. Du, S. Watt, Z. Szilagyi, J. E. Saiz, R. Madabhushi, C. J. Penkett, M. Sipiczki, J. Bahler, et al. Impairment of the TFIIH-associated CDK-activating Kinase Selectively Affects Cell Cycle-regulated Gene Expression in Fission Yeast Mol. Biol. Cell, June 1, 2005; 16(6): 2734 - 2745. [Abstract] [Full Text] [PDF]

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				V. Buck, S. S. Ng, A. B. Ruiz-Garcia, K. Papadopoulou, S. Bhatti, J. M. Samuel, M. Anderson, J. B. A. Millar, and C. J. McInerny Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast J. Cell Sci., November 1, 2004; 117(23): 5623 - 5632. [Abstract] [Full Text] [PDF]

				A. N. Tse and G. K. Schwartz Potentiation of Cytotoxicity of Topoisomerase I Poison by Concurrent and Sequential Treatment with the Checkpoint Inhibitor UCN-01 Involves Disparate Mechanisms Resulting in Either p53-Independent Clonogenic Suppression or p53-Dependent Mitotic Catastrophe Cancer Res., September 15, 2004; 64(18): 6635 - 6644. [Abstract] [Full Text] [PDF]

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				P. R. Andreassen, F. B. Lacroix, O. D. Lohez, and R. L. Margolis Neither p21WAF1 Nor 14-3-3{sigma} Prevents G2 Progression to Mitotic Catastrophe in Human Colon Carcinoma Cells after DNA Damage, But p21WAF1 Induces Stable G1 Arrest in Resulting Tetraploid Cells Cancer Res., October 1, 2001; 61(20): 7660 - 7668. [Abstract] [Full Text] [PDF]

				J. L. Santos and K. Shiozaki Fungal Histidine Kinases Sci. Signal., September 4, 2001; 2001(98): re1 - re1. [Abstract] [Full Text] [PDF]

				S. Tournier and J. B.A. Millar A Role for the START Gene-specific Transcription Factor Complex in the Inactivation of Cyclin B and Cut2 Destruction Mol. Biol. Cell, October 1, 2000; 11(10): 3411 - 3424. [Abstract] [Full Text]

				K. Aoyama, Y. Mitsubayashi, H. Aiba, and T. Mizuno Spy1, a Histidine-Containing Phosphotransfer Signaling Protein, Regulates the Fission Yeast Cell Cycle through the Mcs4 Response Regulator J. Bacteriol., September 1, 2000; 182(17): 4868 - 4874. [Abstract] [Full Text]

				S. Landry, M. T. Pettit, E. Apolinario, and C. S. Hoffman The Fission Yeast git5 Gene Encodes a G{beta} Subunit Required for Glucose-Triggered Adenylate Cyclase Activation Genetics, April 1, 2000; 154(4): 1463 - 1471. [Abstract] [Full Text]

				M. C. Gustin, J. Albertyn, M. Alexander, and K. Davenport MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., December 1, 1998; 62(4): 1264 - 1300. [Abstract] [Full Text] [PDF]

				E. L. Grishchuk, J. L. Howe, and J. R. McIntosh A Screen for Genes Involved in the Anaphase Proteolytic Pathway Identifies tsm1+, a Novel Schizosaccharomyces pombe Gene Important for Microtubule Integrity Genetics, July 1, 1998; 149(3): 1251 - 1264. [Abstract] [Full Text] [PDF]

				M. Umeda, R. P. Bhalerao, J. Schell, H. Uchimiya, and C. Koncz A distinct cyclin-dependent kinase-activating kinase of Arabidopsis thaliana PNAS, April 28, 1998; 95(9): 5021 - 5026. [Abstract] [Full Text] [PDF]

				J C Shieh, M G Wilkinson, V Buck, B A Morgan, K Makino, and J B Millar The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle. Genes & Dev., April 15, 1997; 11(8): 1008 - 1022. [Abstract] [PDF]

				J B Millar, V Buck, and M G Wilkinson Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes & Dev., September 1, 1995; 9(17): 2117 - 2130. [Abstract] [PDF]

				F.O. Fields and J. Thorner Genetic Suppression Analysis of the Function of a Protein Kinase C (PKC1 Gene Product) in Saccharomyces cerevisiae Cell Cycle Progression: The SKCd Mutations Cold Spring Harb Symp Quant Biol, January 1, 1991; 56(0): 51 - 60. [Abstract] [PDF]

				J.D. Hudson, H. Feilotter, C. Lingner, R. Rowley, and P.G. Young stf1: A New Suppressor of the Mitotic Control Gene, cdc25, in Schizosaccharomyces pombe Cold Spring Harb Symp Quant Biol, January 1, 1991; 56(0): 599 - 604. [Abstract] [PDF]

				P.A. Fantes, E. Warbrick, D.A. Hughes, and S.A. MacNeill New Elements in the Mitotic Control of the Fission Yeast Schizosaccharomyces pombe Cold Spring Harb Symp Quant Biol, January 1, 1991; 56(0): 605 - 611. [Abstract] [PDF]