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bioRxiv · 10.1101/2025.10.31.685952

A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation

Meaders, J. L.·Rodriguez, A. A.·Variyar, S.·Park, S.·Cirulli, A. E.·Oegema, K.·Corbett, K. D.·Desai, A.
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Abstract

Accurate chromosome segregation requires dynamic kinetochore-microtubule attachments that, under the regulation of Aurora family kinases, biorient and align replicated chromosomes. In C. elegans, Aurora A acts with the TPX2-related activator TPXL-1 to regulate these attachments and control spindle length. We show that, in addition to prominent spindle pole localization, TPXL-1-AurA has a chromatin-associated pool positioned between the sister kinetochores. Structural modeling and biochemical analysis support TPXL-1 directly recognizing the nucleosome acidic patch via an arginine anchor. Disrupting this interaction selectively removed chromatin-bound TPXL-1-AurA and caused chromosome missegregation, whereas elevation of the chromatin pool disrupted chromosome alignment. These opposing perturbations inversely affected kinetochore recruitment of the microtubule-binding Ska complex. These results support spatially distinct TPXL-1-AurA populations acting sequentially, with the spindle pole pool controlling spindle length by switching kinetochores out of a depolymerization-coupled state, and the chromatin pool controlling attachment stabilization to ensure biorientation prior to anaphase.

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Meaders, J. L., Rodriguez, A. A., Variyar, S., Park, S., Cirulli, A. E., Oegema, K., Corbett, K. D., Desai, A.. 2025-11-01. A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation. https://doi.org/10.1101/2025.10.31.685952

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