The spindle assembly checkpoint (SAC) monitors and promotes kinetochoremicrotubule attachment during mitosis. Bubl and BubRl, SAC components, originated from duplication of an ancestor gene. Subsequent subfunctionalization established subordination: Bubl, recruited first to kinetochores, promotes successive BubRl recruitment. Because both Bubl and BubRl hetero- dimerize with Bub3, a targeting adaptor for phosphorylated kinetochores, the molecular basis for such sub-functionalization is unclear. We demonstrate that Bubl, but not BubRl, enhances binding of Bub3 to phosphorylated kinetochores. Grafting a short motif of Bubl onto BubRl promotes Bubl-independent kinetochore recruitment of BubRl. Such gain-of-function BubRl mutant cannot sustain a functional checkpoint. We demonstrate that kinetochore localization of BubRl relies on direct hetero-dimerization with Bubl at a pseudo-symmetric interface. Such pseudo-symmetric interaction underpins a template-copy relationship crucial for kinetochore-microtubule attachment and SAC signaling. Our results illustrate how gene duplication and sub-functionalization shape the workings of an essential molecular network.

Overlack, K., Primorac, I., Vleugel, M., Krenn, V., Maffini, S., Hoffmann, I., et al. (2015). A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. ELIFE, 2015(4) [10.7554/eLife.05269].

A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint

Krenn, Veronica;
2015

Abstract

The spindle assembly checkpoint (SAC) monitors and promotes kinetochoremicrotubule attachment during mitosis. Bubl and BubRl, SAC components, originated from duplication of an ancestor gene. Subsequent subfunctionalization established subordination: Bubl, recruited first to kinetochores, promotes successive BubRl recruitment. Because both Bubl and BubRl hetero- dimerize with Bub3, a targeting adaptor for phosphorylated kinetochores, the molecular basis for such sub-functionalization is unclear. We demonstrate that Bubl, but not BubRl, enhances binding of Bub3 to phosphorylated kinetochores. Grafting a short motif of Bubl onto BubRl promotes Bubl-independent kinetochore recruitment of BubRl. Such gain-of-function BubRl mutant cannot sustain a functional checkpoint. We demonstrate that kinetochore localization of BubRl relies on direct hetero-dimerization with Bubl at a pseudo-symmetric interface. Such pseudo-symmetric interaction underpins a template-copy relationship crucial for kinetochore-microtubule attachment and SAC signaling. Our results illustrate how gene duplication and sub-functionalization shape the workings of an essential molecular network.
Articolo in rivista - Articolo scientifico
Bub1; Bub3; BubR1; Casc5; Cdc20; Cell cycle; Divergence; Escape from adaptive conflict; Evolution; Gene duplication; Kinetochore; KMN network; Knl1; Mad2; Mis12; Mitotic checkpoint; Mps1; Reversine; Spindle assembly checkpoint; Sub-functionalization;
English
2015
2015
4
e05269
open
Overlack, K., Primorac, I., Vleugel, M., Krenn, V., Maffini, S., Hoffmann, I., et al. (2015). A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. ELIFE, 2015(4) [10.7554/eLife.05269].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/397716
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