Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Hadders, Michael A.; Hindriksen, Sanne; Truong, My Anh; Mhaskar, Aditya N.; Wopken, J Pepijn; Vromans, Martijn J.M.; Lens, Susanne M.A.

doi:10.1083/jcb.201907087

Cited by 84 publications

(105 citation statements)

References 106 publications

(206 reference statements)

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“…In agreement with our results, an accompanying paper from the Lens laboratory also demonstrated that Bub1 and Haspin are individually capable of recruiting the CPC to distinct locations within the kinetochore, and furthermore, they find that neither recruitment pathway is required for kinase activity of Aurora B at kinetochores (Hadders et al, 2020). Interestingly, in their study, CRISPR/Cas9-mediated Haspin knockout combined with Bub1 kinase inhibition resulted in impaired error correction as detected by a monastrol washout assay.…”

Section: Discussionsupporting

confidence: 90%

Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells

Broad

DeLuca

2020

Journal of Cell Biology

101

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Aurora B kinase has a critical role in regulating attachments between kinetochores and spindle microtubules during mitosis. Early in mitosis, kinase activity at kinetochores is high to promote attachment turnover, and in later mitosis, activity decreases to ensure attachment stabilization. Aurora B localizes prominently to inner centromeres, and a population of the kinase is also detected at kinetochores. How Aurora B is recruited to and evicted from these regions to regulate kinetochore-microtubule attachments remains unclear. Here, we identified and investigated discrete populations of Aurora B at the centromere/kinetochore region. An inner centromere pool is recruited by Haspin phosphorylation of histone H3, and a kinetochore-proximal outer centromere pool is recruited by Bub1 phosphorylation of histone H2A. Finally, a third pool resides ~20 nm outside of the inner kinetochore protein CENP-C in early mitosis and does not require either the Bub1/pH2A/Sgo1 or Haspin/pH3 pathway for localization or activity. Our results suggest that distinct molecular pathways are responsible for Aurora B recruitment to centromeres and kinetochores.

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Section: Discussionsupporting

confidence: 90%

Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells

Broad

DeLuca

2020

Journal of Cell Biology

101

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“…Several previous studies have suggested that chromosome localized CPC regulates error correction, bi-orientation, and checkpoint silencing (Andrews et al, 2004;Foley and Kapoor, 2013;Liu et al, 2009;Tanaka et al, 2002), although some of these functions may not require precise centromere localization (Hadders et al, 2020;Hengeveld et al, 2017). However, our analysis of multiple Incenp mutants suggests that chromosomal localization of the CPC does not promote these functions.…”

Section: Regulation Of Homolog Bi-orientation By the Cpccontrasting

confidence: 62%

Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

Wang

Defosse

Jang

et al. 2020

Preprint

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The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosomal passenger complex (CPC), which consists of INCENP, Borealin, Survivin and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and HP1 is crucial for the initial recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. We also found that HP1 moves from the chromosomes to the spindle microtubules along with the CPC, and based on this, propose a mechanism for how the CPC moves from the chromosomes to the microtubules. Within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.

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“…Haspin, a highly conserved kinase in eukaryotes, is responsible for phosphorylation of histone H3T3 during mitosis [16]. Haspin kinase has been shown to be involved in sister chromatid cohesion [17] and to be necessary to localize the Chromosomal Passenger Complex (CPC) on mitotic chromatin at centromeres to activate Aurora B that regulates kinetochore-microtubule attachments [18,19,20]. In fission yeast and mammalian cells, haspin has been shown to bind the cohesin-associated protein Pds5 at centromeres and to antagonize the cohesin-unloading factor Wapl [21,22,23].…”

Section: Introductionmentioning

confidence: 99%

Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing

et al. 2020

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Haspin, a highly conserved kinase in eukaryotes, has been shown to be responsible for phosphorylation of histone H3 at threonine 3 (H3T3ph) during mitosis, in mammals and yeast. Here we report that haspin is the kinase that phosphorylates H3T3 in Drosophila melanogaster and it is involved in sister chromatid cohesion during mitosis. Our data reveal that haspin also phosphorylates H3T3 in interphase. H3T3ph localizes in broad silenced domains at heterochromatin and lamin-enriched euchromatic regions. Loss of haspin compromises insulator activity in enhancer-blocking assays and triggers a decrease in nuclear size that is accompanied by changes in nuclear envelope morphology. We show that haspin is a suppressor of position-effect variegation involved in heterochromatin organization. Our results also demonstrate that haspin is necessary for pairing-sensitive silencing and it is required for robust Polycomb-dependent homeotic gene silencing. Haspin associates with the cohesin complex in interphase, mediates Pds5 binding to chromatin and cooperates with Pds5-cohesin to modify Polycomb-dependent homeotic transformations. Therefore, this study uncovers an unanticipated role for haspin kinase in genome organization of interphase cells and demonstrates that haspin is required for homeotic gene regulation.

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Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Cited by 84 publications

References 106 publications

Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells

Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells

Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing

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