The Bub2p Spindle Checkpoint Links Nuclear Migration with Mitotic Exit

Abstract

Bfa1p and Bub2p are spindle checkpoint proteins that likely have GTPase activation activity and are associated with the budding yeast spindle pole body (SPB). Here, we show that Bfa1p and Bub2p bind the Ras-like GTPase Tem1p, a component of the mitotic exit network, to the cytoplasmic face of the SPB that enters the bud, whereas the GDP/GTP exchange factor Lte1p is associated with the cortex of the bud. Migration of the SPB into the bud probably allows activation of Tem1p through Lte1p, thereby linking nuclear migration with mitotic exit. Since components of the Bub2p checkpoint are conserved in other organisms, we propose that the position of the SPB or mammalian centrosome controls the timing of mitotic exit.

Phosphatase 2A Negatively Regulates Mitotic Exit inSaccharomyces cerevisiae

“…Bfa1 and Bub2 also negatively regulate mitotic exit by forming a complex with Tem1, a key player in the MEN pathway (Pereira et al, 2000). Because Bfa1 is a phosphoprotein and its phosphorylation promotes mitotic exit (Hu et al, 2001), a reasonable model is that PP2A dephosphorylates Bfa1 to inhibit mitotic exit.…”

Yeast polo-like kinases: functionally conserved multitask mitotic regulators

“…A small Ras-like Tem1 GTPase (Geymonat et al, 2002) and its two-component GAPs, Bfa1 and Bub2 (Geymonat et al, 2003), are present at the cytoplasmic side of the SPB that migrates into the bud, whereas Tem1's GTP/GDP exchange factor Lte1 localizes to the bud cortex (Bardin et al, 2000;Pereira et al, 2000). Lte1 localization to the bud cortex is promoted by Cdk1 and Cla4, whereas Lte1 dissociation from the bud cortex is promoted by Cdc14 (Hofken and Schiebel, 2002;Jensen et al, 2002a), perhaps in a positive feedback loop.…”

Human MPS1 Kinase Is Required for Mitotic Arrest Induced by the Loss of CENP-E from Kinetochores

“…MPS1, BUB1, BUB3, MAD1, MAD2, and MAD3 monitor kinetochore microtubule attachments and prevent premature chromosome segregation by inhibiting degradation of securin/Pds1 and mitotic cyclins (Wassmann and Benezra, 2001;Peters, 2002). BUB2 acts along a different pathway that monitors spindle integrity and orientation and prevents premature cytokinesis by inhibiting the degradation of the mitotic cyclin Clb2 (Alexandru et al, 1999;Fesquet et al, 1999;Fraschini et al, 1999;Li, 1999;Bardin et al, 2000;Bloecher et al, 2000;Pereira et al, 2000).…”

“…MPS1, BUB1, BUB3, MAD1, MAD2, and MAD3 monitor kinetochore microtubule attachments and prevent premature chromosome segregation by inhibiting degradation of securin/Pds1 and mitotic cyclins (Wassmann and Benezra, 2001;Peters, 2002). BUB2 acts along a different pathway that monitors spindle integrity and orientation and prevents premature cytokinesis by inhibiting the degradation of the mitotic cyclin Clb2 (Alexandru et al, 1999;Fesquet et al, 1999;Fraschini et al, 1999;Li, 1999;Bardin et al, 2000;Bloecher et al, 2000;Pereira et al, 2000).Many of the mitotic checkpoint genes in yeast are evolutionarily conserved, because orthologues of MAD1, MAD2, MAD3, BUB1, and BUB3 have been identified in worms, flies, and mammals (Chen et al, 1996;Li and Benezra, 1996;Taylor and McKeon, 1997;Basu et al, 1998;Cahill et al, 1998;Chan et al, 1998;Gorbsky et al, 1998;Jablonski et al, 1998;Jin et al, 1998;Taylor et al, 1998;Basu et al, 1999;Kitagawa and Hieter, 2001). Importantly, many of these mitotic checkpoint proteins bind preferentially to unattached kinetochores, where they are postulated to function in generating the "wait anaphase signal" (Hoffman et al, 2001, and references therein).…”