Structure and function of the outer kinetochore

2026-08-03

PRE

Arianna Esposito Verza *

Pim J. Huis in ’t Veld

Rachel R. Brown

Aaron F. Straight *

DOI：10.1038/s41580-026-00988-8

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The kinetochore is the complex molecular machine that controls chromosome segregation. The kinetochore comprises two regions: the inner kinetochore, which assembles on the specialized chromatin structure of the centromere, and the outer kinetochore, the site of microtubule binding and feedback control of mitotic progression. The core of the outer kinetochore is the Knl1–Mis12–Ndc80 (KMN) complex. The KMN binds directly to microtubules, controls the recruitment of additional microtubule binders and modulators, and is the primary switch for the spindle assembly checkpoint, a feedback control mechanism that coordinates mitotic exit with completion of chromosome biorientation. Live-cell imaging analyses of chromosome alignment in mitosis, combined with sophisticated biochemical reconstitutions and high resolution structural analyses, are finally shedding light on the dynamic integration of these activities. In this Review, we focus on how the handful of KMN complexes present at each microtubule-binding site achieves this complex regulation with high accuracy. We refer readers to a complementary Review published in the same issue for a discussion on the structure and function of the inner kinetochore. The kinetochore orchestrates chromosome segregation. The KMN complex, which forms the core of the outer kinetochore binds to microtubules, recruits regulators and functions as a switch for the spindle assembly checkpoint. Recent integrative imaging, biochemical and structural studies have revealed how the KMN assemblies ensure accurate chromosome segregation.

Structure and function of the outer kinetochore

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