Bfa1

Bfa1 is a protein in the budding yeast Saccharomyces cerevisiae that functions as a key regulator of the mitotic exit network (MEN). It forms a GTPase-activating protein (GAP) complex with Bub2, and together they act on Tem1, a small GTPase, to control the timing of mitotic exit. The Bfa1–Bub2 complex inhibits Tem1 by stimulating GTP hydrolysis, thereby delaying MEN activation until the appropriate cell-cycle and spatial cues are met.

Localization and mechanism play central roles in its function. The Bfa1–Bub2 complex localizes to spindle pole bodies (SPBs) and shows dynamic distribution during the cell cycle, with enrichment on the daughter-bound SPB during anaphase. This spatial regulation contributes to the spindle position checkpoint, ensuring that mitotic exit occurs only after the spindle is correctly oriented and partially segregated.

Regulation of Bfa1 activity involves multiple cell-cycle cues. The complex is subject to phosphorylation by kinases such as Cdk1 (Cdc28) and Cdc5, which help maintain Tem1 inhibition during early mitosis. Inactivation of this inhibition, and thus activation of Tem1, is promoted later by processes including dephosphorylation by Cdc14 and the action of Lte1 in the bud, which supports Tem1 activation when the spindle enters the daughter cell.

Genetic and cellular significance are underscored by Bfa1’s role in the spindle position checkpoint. Deletion or impairment of BFA1 or its partner Bub2 can lead to defects in SPOC and mis-timed mitotic exit, increasing the risk of chromosome mis-segregation and aneuploidy. Bfa1 thus serves as a critical control point linking spindle orientation with cell-cycle progression. See also Bub2, Tem1, Lte1, MEN, SPOC.