Abstract

In eukaryotic cells, mitosis is regulated by so-called mitotic checkpoint controls. These controls ensure that mitosis does not occur until the genome is fully replicated and also contains no double-stranded DNA breaks. The checkpoint pathways thus assure that each daughter cell will contain a full copy of the parental genotype. Checkpoint controls are well characterized in fission yeast in which mitotic controls involve the M- phase enzyme (cdc2/cyclin B) and antagonistically functioning kinases (wee1/mik1) and phosphatases (cdc25) that regulate cdc2. The broad long- term objective of this proposal is to understand the mitotic checkpoint control pathways of human cells. This will involve not only the isolation of checkpoint control genes and characterization of their protein products, but also investigation of checkpoints as integrated control functions. These studies are significant for human proliferative disease because tumor cells display deficiencies in checkpoint controls and these deficiencies may be related to the relative efficacy of chemotherapeutic agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM039620-06
Application #
3296760
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-02-01
Project End
1997-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724

  Publications

Okamoto, K; Kamibayashi, C; Serrano, M et al. (1996) p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A. Mol Cell Biol 16:6593-602
Demetrick, D J; Zhang, H; Beach, D H (1996) Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2). Cytogenet Cell Genet 73:104-7
Casso, D; Beach, D (1996) A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 252:518-29
Demetrick, D J; Zhang, H; Beach, D H (1996) Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22. Cytogenet Cell Genet 73:250-4
Zhang, H; Kobayashi, R; Galaktionov, K et al. (1995) p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell 82:915-25
Demetrick, D J; Matsumoto, S; Hannon, G J et al. (1995) Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3). Cytogenet Cell Genet 69:190-2
Demetrick, D J; Zhang, H; Beach, D H (1994) Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes. Cytogenet Cell Genet 66:72-4
Okamoto, K; Beach, D (1994) Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J 13:4816-22
Demetrick, D J; Beach, D H (1993) Chromosome mapping of human CDC25A and CDC25B phosphatases. Genomics 18:144-7
Zhang, H; Xiong, Y; Beach, D (1993) Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell 4:897-906

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