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XB-ART-56297
J Cell Biol January 1, 2019; 218 (10): 3237-3257.

Enrichment of Aurora B kinase at the inner kinetochore controls outer kinetochore assembly.

Bonner MK , Haase J , Swinderman J , Halas H , Miller Jenkins LM , Kelly AE .


Abstract
Outer kinetochore assembly enables chromosome attachment to microtubules and spindle assembly checkpoint (SAC) signaling in mitosis. Aurora B kinase controls kinetochore assembly by phosphorylating the Mis12 complex (Mis12C) subunit Dsn1. Current models propose Dsn1 phosphorylation relieves autoinhibition, allowing Mis12C binding to inner kinetochore component CENP-C. Using Xenopus laevis egg extracts and biochemical reconstitution, we found that autoinhibition of the Mis12C by Dsn1 impedes its phosphorylation by Aurora B. Our data indicate that the INCENP central region increases Dsn1 phosphorylation by enriching Aurora B at inner kinetochores, close to CENP-C. Furthermore, centromere-bound CENP-C does not exchange in mitosis, and CENP-C binding to the Mis12C dramatically increases Dsn1 phosphorylation by Aurora B. We propose that the coincidence of Aurora B and CENP-C at inner kinetochores ensures the fidelity of kinetochore assembly. We also found that the central region is required for the SAC beyond its role in kinetochore assembly, suggesting that kinetochore enrichment of Aurora B promotes the phosphorylation of other kinetochore substrates.

PubMed ID: 31527147
PMC ID: PMC6781445
Article link: J Cell Biol

Genes referenced: birc5 bub1b cdca8 dsn1 incenp mad2l1 mis12 ndc80 picalml


Article Images: [+] show captions
References [+] :
Abe, HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors. 2016, Pubmed


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