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cdc2 and the regulation of mitosis: six interacting mcs genes
Abstract:
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, wee 1, 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.
Insights
Researchers identified six new mitotic catastrophe suppressor (mcs) genes in fission yeast by studying a lethal double mutant. These genes interact with cell cycle regulators, revealing new elements in mitosis control.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Fission yeast mutants (cdc2-3w weel-50) exhibit temperature-sensitive lethality due to mitotic catastrophe, characterized by chromosome segregation errors.
- Understanding the regulation of mitosis is crucial for cell cycle control and preventing genomic instability.
Purpose of the Study:
- To identify novel genetic factors involved in the regulation of mitosis by isolating suppressors of a temperature-sensitive lethal fission yeast mutant.
- To characterize the function and genetic interactions of these newly identified mitotic catastrophe suppressor (mcs) genes.
Main Methods:
- Isolation and characterization of revertants from a cdc2-3w weel-50 double mutant.
- Genetic analysis of suppressor mutations, including complementation tests and double mutant construction.
- Phenotypic analysis of single and double mutants to assess cell cycle progression and mitotic fidelity.
Main Results:
- Six new mitotic catastrophe suppressor (mcs) genes were identified, which are not allelic to known mitotic control genes.
- mcs mutations are recessive and do not cause lethality as single mutants.
- Diverse genetic interactions were observed between mcs genes and other cell cycle regulators (e.g., cdc2, cdc25, wee1), affecting phenotypes like cell cycle arrest and lethality.
Conclusions:
- The identified mcs genes represent novel components of the mitotic regulatory network in fission yeast.
- These genes may function as activators or substrates of the cdc2 protein kinase, providing new insights into mitosis control.
- Further research into mcs genes can elucidate fundamental mechanisms of cell division and chromosome segregation.