Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle

The Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin an...

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Main Authors: Serena, M, Nunes Bastos, R, Elliott, PR, Barr, FA
Format: Journal article
Language:English
Published: Rockefeller University Press 2020
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author Serena, M
Nunes Bastos, R
Elliott, PR
Barr, FA
author_facet Serena, M
Nunes Bastos, R
Elliott, PR
Barr, FA
author_sort Serena, M
collection OXFORD
description The Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase.
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spelling oxford-uuid:8fe97f61-4e7e-42c0-b864-e0f9ad7105852022-03-26T23:07:51ZMolecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindleJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8fe97f61-4e7e-42c0-b864-e0f9ad710585EnglishSymplectic ElementsRockefeller University Press2020Serena, MNunes Bastos, RElliott, PRBarr, FAThe Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase.
spellingShingle Serena, M
Nunes Bastos, R
Elliott, PR
Barr, FA
Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title_full Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title_fullStr Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title_full_unstemmed Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title_short Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle
title_sort molecular basis of mklp2 dependent aurora b transport from chromatin to the anaphase central spindle
work_keys_str_mv AT serenam molecularbasisofmklp2dependentaurorabtransportfromchromatintotheanaphasecentralspindle
AT nunesbastosr molecularbasisofmklp2dependentaurorabtransportfromchromatintotheanaphasecentralspindle
AT elliottpr molecularbasisofmklp2dependentaurorabtransportfromchromatintotheanaphasecentralspindle
AT barrfa molecularbasisofmklp2dependentaurorabtransportfromchromatintotheanaphasecentralspindle