Practice question

Attachment of spindle microtubules to chromosomes occurs via kinetochore, megadalton protein assembly built on centromeric CENP-A chromatin. Outer kinetochore KMN network provides primary microtubule interface. Ndc80 complex heterotetramer Ndc80, Nuf2, Spc24, Spc25 extends 55 nm, with calponin homology domains at Ndc80-Nuf2 binding microtubule lattice electrostatically, while Spc24-Spc25 anchors to inner kinetochore Mis12 complex. Affinity modulated by Aurora B phosphorylation at Ndc80 tail reducing binding upon low tension to facilitate error correction. In budding yeast, Dam1 complex decamer forms 16-member ring encircling microtubule, tracking depolymerizing ends through biased diffusion and providing processive coupling, essential for chromosome movement. Humans employ Ska complex of Ska1-3 as functional analog forming additional microtubule binding module and recruiting APC/C. Aurora B at inner centromere phosphorylates components when tension low, destabilizing faulty contacts, while PP1 and PP2A-B56 opposing phosphatases recruited after tension generated stabilize correct amphitelic orientation, ensuring equal segregation before separase activation and anaphase progression. This regulatory circuit illustrates integration of checkpoint kinases, ubiquitin ligases, phosphatases and structural proteins coordinating accurate cell division and preventing aneuploidy associated with tumorigenesis.