The spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance mechanism that delays anaphase onset and mitotic exit in response to the lack of kinetochore attachment. Target of the SAC is the E3 ubiquitin ligase anaphase promoting complex (APC) bound to its Cdc20 activator. The Cdc20/APC complex is in turn required for sister chromatid separation and mitotic exit through ubiquitin-mediated proteolysis of securin, thus relieving inhibition of separase that unties sister chromatids. Separase is also involved in the FEAR (Cdc-fourteen early anaphase release) pathway of nucleolar release and activation of the Cdc14 phosphatase, which regulates several microtubule-linked processes at the metaphase/anaphase transition and also drives mitotic exit. Here we report that the SAC prevents separation of microtubule-organizing centers (spindle pole bodies, SPBs) when spindle assembly is defective. Under these circumstances, failure of SAC activation causes unscheduled SPB separation, which requires Cdc20/APC, the FEAR pathway, cytoplasmic dynein and the actin cytoskeleton. We propose that, besides inhibiting sister chromatid separation, the SAC preserves the accurate transmission of chromosomes also by preventing SPBs to migrate far apart until the conditions to assemble a bipolar spindle are satisfied.

Chiroli, E., Rancati, G., Catusi, I., Lucchini, G., Piatti, S. (2009). Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. MOLECULAR BIOLOGY OF THE CELL, 20(10), 2626-2637 [10.1091/mcb.E08-11-1150].

Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast

LUCCHINI, GIOVANNA;PIATTI, SIMONETTA
2009

Abstract

The spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance mechanism that delays anaphase onset and mitotic exit in response to the lack of kinetochore attachment. Target of the SAC is the E3 ubiquitin ligase anaphase promoting complex (APC) bound to its Cdc20 activator. The Cdc20/APC complex is in turn required for sister chromatid separation and mitotic exit through ubiquitin-mediated proteolysis of securin, thus relieving inhibition of separase that unties sister chromatids. Separase is also involved in the FEAR (Cdc-fourteen early anaphase release) pathway of nucleolar release and activation of the Cdc14 phosphatase, which regulates several microtubule-linked processes at the metaphase/anaphase transition and also drives mitotic exit. Here we report that the SAC prevents separation of microtubule-organizing centers (spindle pole bodies, SPBs) when spindle assembly is defective. Under these circumstances, failure of SAC activation causes unscheduled SPB separation, which requires Cdc20/APC, the FEAR pathway, cytoplasmic dynein and the actin cytoskeleton. We propose that, besides inhibiting sister chromatid separation, the SAC preserves the accurate transmission of chromosomes also by preventing SPBs to migrate far apart until the conditions to assemble a bipolar spindle are satisfied.
Articolo in rivista - Articolo scientifico
spindle assembly checkpoint, Cdc14, spindle pole body, sister chromatid separation, genome integrity
English
2626
2637
Chiroli, E., Rancati, G., Catusi, I., Lucchini, G., Piatti, S. (2009). Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. MOLECULAR BIOLOGY OF THE CELL, 20(10), 2626-2637 [10.1091/mcb.E08-11-1150].
Chiroli, E; Rancati, G; Catusi, I; Lucchini, G; Piatti, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/6873
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