One of the hallmarks of cancer cells is loss of control of the cell cycle, leading to uncontrolled cellular division. Paramount to understanding the mechanisms involved in the uncontrolled cellular proliferation of cancer cells is understanding the mechanisms that control the cell division cycle. The objectives of this proposal are to identify and characterize genes involved in controlling cell division. Aspergillus nidulans is used as a model system for these studies: it is simple, easy to manipulate genetically, and many specific cell cycle mutants are available. In this work, genes involved in cell cycle control will be identified by the generation and characterization of extragenic suppressors of nimXcdc2 mutations. nimXcdc2 controls two specific transitions in the A. nidulans cell cycle, the G1/S transition and the G2/M transition, as well as controlling events during S phase. Because extragenic suppressors frequently encode proteins that interact with the original mutant protein, genes which are important for either the G1/S or G2/M transitions or S phase will be identified. The nimXcdc2 mutant strains have been mutagenized and survivors selected for reversion of the mutant phenotype. 17 revertants which contain extragenic suppressor mutations have been identified by genetic analysis and are being characterized for dominance/recessiveness of the mutations. They will then be analyzed to determine if any of the suppressors are allelic or if they contain mutations in previously identified cell cycle control genes in Aspergillus. Novel, non-allelic suppressors will be phenotypically characterized and linkage group determined. These experiments will provide new information on genes that control the eukaryotic cell cycle and will generate strains which will be used for cloning these genes.
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| McGuire, S L; Roe, D L; Carter, B W et al. (2000) Extragenic suppressors of the nimX2(cdc2) mutation of Aspergillus nidulans affect nuclear division, septation and conidiation. Genetics 156:1573-84 |
