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Vol. 19, Issue 10, 4328-4340, October 2008

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Different Levels of Bfa1/Bub2 GAP Activity Are Required to Prevent Mitotic Exit of Budding Yeast Depending on the Type of Perturbations

Department of Biochemistry and Institute of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea

Submitted February 14, 2008; Revised July 22, 2008; Accepted July 23, 2008
Monitoring Editor: Tim Stearns

In budding yeast, Tem1 is a key regulator of mitotic exit. Bfa1/Bub2 stimulates Tem1 GTPase activity as a GTPase-activating protein (GAP). Lte1 possesses a guanine-nucleotide exchange factor (GEF) domain likely for Tem1. However, recent observations showed that cells may control mitotic exit without either Lte1 or Bfa1/Bub2 GAP activity, obscuring how Tem1 is regulated. Here, we assayed BFA1 mutants with varying GAP activities for Tem1, showing for the first time that Bfa1/Bub2 GAP activity inhibits Tem1 in vivo. A decrease in GAP activity allowed cells to bypass mitotic exit defects. Interestingly, different levels of GAP activity were required to prevent mitotic exit depending on the type of perturbation. Although essential, more Bfa1/Bub2 GAP activity was needed for spindle damage than for DNA damage to fully activate the checkpoint. Conversely, Bfa1/Bub2 GAP activity was insufficient to delay mitotic exit in cells with misoriented spindles. Instead, decreased interaction of Bfa1 with Kin4 was observed in BFA1 mutant cells with a defective spindle position checkpoint. These findings demonstrate that there is a GAP-independent surveillance mechanism of Bfa1/Bub2, which, together with the GTP/GDP switch of Tem1, may be required for the genomic stability of cells with misaligned spindles.

Address correspondence to: Kiwon Song (bc5012{at}yonsei.ac.kr)

Abbreviations used: Bfa1-DR, Bfa1-direct repeat; GAP, GTPase-activating protein; GEF, guanine-nucleotide exchange factor; GFP, green fluorescent protein; GST, glutathione S-transferase; GTPase, guanine triphosphatase; MBP, maltose-binding protein; MEN, mitotic exit network; MESG, 2-amino-6-mercapto-7-methylpurine riboside; PAP, peroxidase anti-peroxidase.

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