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Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints
1Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Cell
|December 6, 2001
Summary
Polo/Cdc5 kinase antagonizes Bfa1/Bub2 to promote mitotic exit. Cell cycle checkpoints regulate Bfa1 phosphorylation, ensuring mitotic arrest when DNA damage occurs.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Tem1 GTPase initiates mitotic exit via a signal transduction pathway.
- The Bfa1/Bub2 complex antagonizes Tem1 function throughout most of the cell cycle.
- Regulation of the Bfa1/Bub2 complex is not fully understood.
Purpose of the Study:
- To investigate the upstream regulators of the Bfa1/Bub2 complex.
- To elucidate how Bfa1/Bub2 is controlled by cell cycle checkpoints.
- To understand the role of Polo/Cdc5 kinase in the mitotic exit network.
Main Methods:
- Investigated the interaction between Polo/Cdc5 kinase and Bfa1/Bub2.
- Analyzed the effect of Cdc5 on Bfa1 phosphorylation.
- Examined Bfa1 regulation by spindle assembly and spindle orientation checkpoints.
- Studied the impact of DNA damage on Bfa1 modification via Rad53 and Dun1.
Main Results:
- Polo/Cdc5 kinase phosphorylates Bfa1, antagonizing its function and promoting mitotic exit.
- Spindle assembly and spindle orientation checkpoints inhibit Bfa1 phosphorylation.
- DNA damage induces a Rad53- and Dun1-dependent modification of Bfa1, independent of inhibitory phosphorylation.
- Bfa1 regulation by Cdc5 and checkpoints is crucial for ensuring mitotic arrest.
Conclusions:
- Polo/Cdc5 kinase is an upstream regulator of Bfa1/Bub2 in the mitotic exit pathway.
- Bfa1 phosphorylation is differentially regulated by cell cycle checkpoints and DNA damage.
- Bfa1 modification by multiple pathways is a key mechanism for ensuring proper mitotic arrest.
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