Kinetokoren

Kinetochores (kinetokoren) are multiprotein structures located at the centromeres of chromosomes in most eukaryotic cells. They form the critical link between chromosomes and the spindle apparatus, enabling proper alignment and segregation during cell division, including mitosis and meiosis.

The kinetochore is organized into inner and outer components. The centromeric chromatin contains the histone variant CENP-A, around which the inner kinetochore assembles. The outer kinetochore includes the KMN network, composed of the Knl1 complex, the Mis12 complex, and the Ndc80 complex. The Ndc80 complex is a primary microtubule-binding unit, while other proteins recruit motor enzymes and checkpoint factors, collectively coordinating attachment to spindle microtubules.

Functionally, kinetochores mediate the capture of dynamic microtubules and generate force for chromosome movement. Attachments are stabilized as sister kinetochores become bi-oriented, producing tension that helps ensure correct segregation. Motor proteins such as CENP-E and dynein contribute to chromosome congression and movement along microtubules, while the depolymerizing ends of microtubules can pull chromosomes toward poles.

Regulation is essential to fidelity. The spindle assembly checkpoint monitors kinetochore attachments and prevents anaphase onset until all chromosomes achieve proper bi-orientation. Aurora B kinase and other checkpoint kinases regulate attachment stability and correct erroneous connections, ensuring genome integrity during cell division.

Clinical relevance includes links between kinetochore dysfunction and aneuploidy, cancer, and developmental disorders. Ongoing research investigates kinetochore components as potential targets for therapeutic intervention and as markers of chromosomal instability in disease.