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

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Authors: Johnathan L. Meaders, Alyssa A. Rodriguez, Smriti Variyar, Sung‐Woo Park, Alessandro E. Cirulli, Karen Oegema, Kevin D. Corbett, Arshad B. Desai
Cited by: 0
References: 33

Abstract

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.

Fields of Study & Subjects

Microtubule and mitosis dynamics DNA Repair Mechanisms Chromosomal and Genetic Variations

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
19
Pages
eaed5283–eaed5283
Publication date
6 May 2026
Language
EN