MIS12

Mis12 is a conserved protein complex located at the kinetochore, where it acts as a central scaffold within the KMN network (Knl1-Mis12-Ndc80) that mediates attachment between chromosomes and spindle microtubules during mitosis. The complex helps connect inner kinetochore components to outer microtubule-binding elements, enabling proper chromosome alignment and segregation.

The Mis12 complex is composed of four core subunits. In many organisms these are Mis12 (MIS12), Dsn1 (DSN1), Nnf1 (NNF1), and Nsl1 (NSL1). In budding yeast the functional homologs are Mtw1, Dsn1, Nnf1, and Nsl1. The subunits form a stable, elongated structure that serves as a scaffold for recruitment and stabilization of outer kinetochore components, including the Ndc80 complex and the Knl1 complex.

Function and interactions: The Mis12 complex anchors the outer kinetochore to the centromeric region and facilitates robust microtubule attachment, contributing to the force transmission required for chromosome movement. It also participates in spindle assembly checkpoint signaling by coordinating with other kinetochore proteins to monitor proper microtubule attachment and tension. The activity and localization of Mis12 are coordinated through cell cycle–regulated phosphorylation, ensuring timely assembly of the outer kinetochore as cells enter mitosis.

Importance: The Mis12 complex is essential for accurate chromosome segregation. Loss or dysfunction of its subunits leads to defective kinetochore-microtubule attachments, chromosome misalignment, aneuploidy, and cell cycle arrest or cell death in many species. Its conserved nature makes it a focal point in studies of kinetochore structure and function across eukaryotes.