The Aspergillus nidulans bimE (blocked-in-mitosis) gene encodes multiple cell cycle functions involved in mitotic checkpoint control and mitosis
Autor: | N R Morris, Peter M. Mirabito, Peter C. Scacheri, S.W. James |
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Rok vydání: | 1995 |
Předmět: |
G2 Phase
Cell cycle checkpoint Gene Expression Mitosis Cell Cycle Proteins medicine.disease_cause Aspergillus nidulans Fungal Proteins Cyclins CDC2 Protein Kinase medicine DNA Fungal Interphase Mutation Cyclin-dependent kinase 1 DNA synthesis biology Cell Cycle Temperature Epistasis Genetic Cell Biology G2-M DNA damage checkpoint Cell cycle Flow Cytometry biology.organism_classification Cell biology Phenotype Mutagenesis |
Zdroj: | Journal of Cell Science. 108:3485-3499 |
ISSN: | 1477-9137 0021-9533 |
DOI: | 10.1242/jcs.108.11.3485 |
Popis: | The bimE (blocked-in-mitosis) gene appears to function as a negative mitotic regulator because the recessive bimE7 mutation can override certain interphase-arresting treatments and mutations, causing abnormal induction of mitosis. We have further investigated the role of bimE in cell cycle checkpoint control by: (1) coordinately measuring mitotic induction and DNA content of bimE7 mutant cells; and (2) analyzing epistasis relationships between bimE7 and 16 different nim mutations. A combination of cytological and flow cytometric techniques was used to show that bimE7 cells at restrictive temperature (44 degrees C) undergo a normal, although somewhat slower cell cycle prior to mitotic arrest. Most bimE7 cells were fully reversible from restrictive temperature arrest, indicating that they are able to enter mitosis normally, and therefore require bimE function in order to finish mitosis. Furthermore, epistasis studies between bimE7 and mutations in cdc2 pathway components revealed that the induction of mitosis caused by inactivation of bimE requires functional p34cdc2 kinase, and that mitotic induction by bimE7 depends upon several other nim genes whose functions are not yet known. The involvement of bimE in S phase function and mitotic checkpoint control was suggested by three lines of evidence. First, at restrictive temperature the bimE7 mutation slowed the cell cycle by delaying the onset or execution of S phase. Second, at permissive temperature (30 degrees C) the bimE7 mutation conferred enhanced sensitivity to the DNA synthesis inhibitor hydroxyurea. Finally, the checkpoint linking M phase to the completion of S phase was abolished when bimE7 was combined with two nim mutations that cause arrest in G1 or S phase. A model for bimE function based on these findings is presented. |
Databáze: | OpenAIRE |
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