kinetochores

A kinetochore is a protein structure that forms at the centromere of each chromosome and serves as the attachment site for spindle microtubules during mitosis and meiosis. It functions as the primary interface between chromosomes and the dynamic mitotic spindle, translating microtubule movements into chromosome movement and providing a platform for regulatory signals that ensure accurate segregation.

The kinetochore has a layered architecture. The inner kinetochore interfaces with centromeric chromatin, which contains the histone H3 variant CENP-A and other centromere-associated proteins. The outer kinetochore contains the KMN network—comprising the Knl1 complex, the Mis12 complex, and the Ndc80 complex—which directly binds microtubules. Additional protein assemblies, such as the Dam1/DASH complex in yeast and the Ska complex in vertebrates, aid microtubule engagement in particular organisms. The kinetochore also hosts components of the spindle assembly checkpoint and other regulatory factors that monitor attachment status and tension.

Functionally, kinetochores capture and stabilize microtubules, maintain end-on attachments, and drive chromosome movement as microtubules grow or shrink. Tension generated by bipolar attachments helps stabilize correct bi-orientation, while improper attachments are corrected in part by Aurora B kinase signaling. The spindle assembly checkpoint, involving proteins such as Mps1 and Bub kinases, delays anaphase until all chromosomes are properly attached and under tension.

Kinetochore composition and centromere organization vary among organisms, ranging from point centromeres to regional and holocentric chromosomes. Despite this diversity, kinetochores are essential for accurate chromosome segregation and genomic stability.