Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers

Štimac, Valentina; Koprivec, Isabella; Manenica, Martina; Simunić, Juraj; Tolić, Iva M. (2022) Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers. eLife, 11 . ISSN 2050-084X

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Official URL: https://elifesciences.org/articles/83287

Abstract

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects distinct microtubule classes and thereby mitotic fidelity. Here, we use superresolution microscopy to analyze the previously indistinguishable microtubule arrangements within the crowded metaphase plate area and demonstrate that augmin is vital for the formation of uniformly arranged parallel units consisting of sister kinetochore fibers connected by a bridging fiber. This ordered geometry helps both prevent and resolve merotelic attachments. Whereas augmin-nucleated bridging fibers prevent merotelic attachments by creating a nearly parallel and highly bundled microtubule arrangement unfavorable for creating additional attachments, augmin-nucleated k-fibers produce robust force required to resolve errors during anaphase. STED microscopy revealed that bridging fibers were impaired twice as much as k-fibers following augmin depletion. The complete absence of bridging fibers from a significant portion of kinetochore pairs, especially in the inner part of the spindle, resulted in the specific reduction of the interkinetochore distance. Taken together, we propose a model where augmin promotes mitotic fidelity by generating assemblies consisting of bridging and kinetochore fibers that align sister kinetochores to face opposite poles, thereby preventing erroneous attachments.

Item Type:

Article

Uncontrolled Keywords:

Augmin ; Microtubules ; Aneuploidy

Subjects:

NATURAL SCIENCES > Biology
NATURAL SCIENCES > Interdisciplinary Natural Sciences

Divisions:

Division of Molecular Biology

Projects:

Project title	Project leader	Project code	Project type
Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretena	Tolić, Iva	PZS-2019-02-7653	HRZZ
Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivima	Tolić, Iva; Pavin, Nenad	855158	EK
Nova klasa mikrotubula u vretenu koja djeluje silama na kinetohore	Tolić, Iva	647077	EK
Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomedicini	Tolić, Iva Marija	KK.01.1.1.04.0057	EK