Mitosis and its regulation are of fundamental importance to understanding cell biology, cancer, and human development. The morphological and biochemical features of mitosis are highly conserved among eukaryotic organisms. For this reason the use of lower eukaryotes, e.g. yeasts and fungi to study the genetics of mitosis has been highly productive. Here we propose to study the bimE gene of Aspergillus and its gene product, which has been shown in previous experiments to be an important negative regulator of mitosis and appears to be part of a regulatory system that prevents mitosis if DNA synthesis has not been completed. We will generate and use antibodies to bimE/E. coli trypE or lacZ fusion proteins to characterize the bimE gene product through the cell cycle in synchronized cells, looking for changes in its synthesis, biochemical structure, post- translational modification, localization and interactions with other proteins. We also propose to characterize proteins with which the bimE protein might interact by analysis of indirect suppressor and unlinked noncomplementing mutations. We will attempt to learn how bimE regulates the level of nimA mRNA by determining the effect of bimE on transcription and/or stability of nimA mRNA. Finally, in collaboration with Dr. John Newport of UC-San Diego we will look for a functional homolog of bimE in Xenopus laevis nad study the effect of the bimE gene product on mitosis in the Xenopus egg cytoplasm cell-free system.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034711-09
Application #
3286176
Study Section
Genetics Study Section (GEN)
Project Start
1985-08-01
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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Xiang, X; Osmani, A H; Osmani, S A et al. (1995) Analysis of nuclear migration in Aspergillus nidulans. Cold Spring Harb Symp Quant Biol 60:813-9
Beckwith, S M; Roghi, C H; Morris, N R (1995) The genetics of nuclear migration in fungi. Genet Eng (N Y) 17:165-80
Chiu, Y H; Morris, N R (1995) Extragenic suppressors of nudC3, a mutation that blocks nuclear migration in Aspergillus nidulans. Genetics 141:453-64
Willins, D A; Xiang, X; Morris, N R (1995) An alpha tubulin mutation suppresses nuclear migration mutations in Aspergillus nidulans. Genetics 141:1287-98
James, S W; Mirabito, P M; Scacheri, P C et al. (1995) The Aspergillus nidulans bimE (blocked-in-mitosis) gene encodes multiple cell cycle functions involved in mitotic checkpoint control and mitosis. J Cell Sci 108 ( Pt 11):3485-99
Osmani, A H; van Peij, N; Mischke, M et al. (1994) A single p34cdc2 protein kinase (encoded by nimXcdc2) is required at G1 and G2 in Aspergillus nidulans. J Cell Sci 107 ( Pt 6):1519-28
O'Connell, M J; Meluh, P B; Rose, M D et al. (1993) Suppression of the bimC4 mitotic spindle defect by deletion of klpA, a gene encoding a KAR3-related kinesin-like protein in Aspergillus nidulans. J Cell Biol 120:153-62
Mirabito, P M; Morris, N R (1993) BIMA, a TPR-containing protein required for mitosis, localizes to the spindle pole body in Aspergillus nidulans. J Cell Biol 120:959-68
Morris, N R; Enos, A P (1992) Mitotic gold in a mold: Aspergillus genetics and the biology of mitosis. Trends Genet 8:32-7

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