Author response: Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis

Wike, Candice L.; Graves, Hillary K.; Hawkins, Reva; Gibson, Matthew D.; Ferdinand, Michelle B.; Zhang, Tao; Chen, Zhihong; Hudson, Damien F.; Ottesen, Jennifer J.; Poirier, Michael G.; Schumacher, Jill M.; Tyler, Jessica K.

doi:10.7554/elife.11402.029

2016

DOI: 10.7554/elife.11402.029

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Author response: Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis

Candice L. Wike

Hillary K. Graves

Reva Hawkins

et al.

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2021

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“…When we evaluated the levels of REC8, a meiosis-specific cohesin subunit, in Aurka KO oocytes treated with reversine, we found that chromosome-localized REC8 was only reduced by ~ 35%(Fig.6H-I). These data suggest that AURKA regulates the cleavage of cohesin in an APC/Cindependent manner as it does in mitotic cells[41].Therefore, these data demonstrate that the SAC is not the sole mediator of the Met I arrest in Aurka KO oocytes. In summary, we conclude that AURKA is the only Aurora kinase in mouse oocytes that is essential for fertility and MI [28, 29] (Fig.…”

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Aurora kinase A is essential for meiosis in mouse oocytes

Blengini

Ibrahimian

Vaškovičová

et al. 2021

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The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile and their oocytes fail to complete meiosis I. In determining the AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at microtubule organizing centers (MTOCs; meiotic spindle poles). This activation induces fragmentation of the MTOCs, a step essential for building a bipolar spindle. The next step that requires AURKA is building the liquid-like spindle domain that involves TACC3. Finally, we find that AURKA is also required for anaphase I onset to trigger cohesin cleavage in an APC/C independent manner. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.Author SummaryFemale gametes, oocytes, are uniquely prone to chromosome segregation errors in meiosis I that are associated with early miscarriages. The Aurora protein kinases are essential to control chromosome segregation in all cell types. During mitosis, Aurora kinase A (AURKA) regulates the building of the spindle, the machinery responsible for pulling chromosomes apart. Here, we use a genetic approach to demonstrate that AURKA is essential for meiosis I in mouse oocytes. AURKA is required at multiple steps in meiosis I, first to trigger fragmentation of protein structures that make up the two ends of the meiotic spindle, later to regulate building of a specialized phase-separated spindle domain, and finally to trigger efficient cleavage of cohesin, the molecular glue that holds chromosomes together until anaphase onset. These findings are the first demonstration of distinct Aurora kinase function that cannot be compensated for by the other two homologs. Therefore, this mouse model is excellent tool for pinpointing specific Aurora kinase functions and identifying AURKA target proteins critical for chromosome segregation in meiosis I.

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confidence: 73%

Aurora kinase A is essential for meiosis in mouse oocytes

Blengini

Ibrahimian

Vaškovičová

et al. 2021

Preprint

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Author response: Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis

Cited by 1 publication

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Aurora kinase A is essential for meiosis in mouse oocytes

Aurora kinase A is essential for meiosis in mouse oocytes

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