Bub2Bfa1

Bub2Bfa1 refers to the Bub2–Bfa1 heterodimer, a conserved protein complex in budding yeast (Saccharomyces cerevisiae) that regulates the timing and placement of mitotic exit. The complex consists of Bub2, a GTPase-activating protein, and Bfa1, its partner, and it localizes to spindle pole bodies throughout the cell cycle.

Functionally, Bub2–Bfa1 acts as a key inhibitor of the Mitotic Exit Network (MEN) by acting as a GAP for Tem1, a small GTPase that triggers mitotic exit. When Bub2–Bfa1 maintains Tem1 in its GDP-bound state, MEN remains inactive, delaying exit from mitosis. Activation of Tem1 and the MEN occurs only under appropriate conditions, such as correct spindle positioning and bud-directed cues, allowing timely progression to cytokinesis.

Regulation of Bub2–Bfa1 is integrated with the spindle position checkpoint. Kin4 kinase promotes maintenance of Bub2–Bfa1 activity when the spindle is misaligned, while Cdc5 kinase–dependent phosphorylation modulates Bub2–Bfa1 to permit Tem1 activation in late mitosis. Lte1, a guanine nucleotide exchange factor located in the budding daughter cell, also contributes to activating Tem1 when the spindle is properly oriented toward the bud. The coordinated regulation ensures that mitotic exit occurs only after proper spindle orientation and chromosome segregation.

Disruption of Bub2 or Bfa1 alters the timing of mitotic exit and can lead to premature or delayed exit and potential chromosome missegregation. Bub2–Bfa1 serves as a model for studying checkpoint signaling and the spatial control of key cell cycle transitions in yeast.