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

Created on 02 Nov 2025

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Nov 2025.

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