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.
Original language | English |
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Article number | e05269 |
Journal | eLife |
Volume | 2015 |
Issue number | 4 |
DOIs | |
Publication status | Published - Jan 22 2015 |
Keywords
- 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
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Medicine(all)
- Neuroscience(all)