Practice question

Prometaphase is transitional stage converting interphase nuclear architecture to mitotic spindle structure, initiated by rising cyclin B-CDK1 activity. CDK1 phosphorylates lamins A/C and B at serine residues within tail domain, causing depolymerization of filamentous lamina and fragmentation of nuclear envelope into vesicles merging with endoplasmic reticulum. Condensed chromosomes consisting of two sister chromatids embraced by cohesin are released into cytoplasm. Concurrently, kinetochores assembled at centromeres containing CENP-A nucleosomes fully mature, forming outer plate with KMN network composed of KNL1 scaffold, Mis12 complex, and Ndc80 complex that directly binds microtubule plus ends with high affinity. Motor proteins CENP-E kinesin and dynein mediate initial lateral capture of highly dynamic microtubules emanating from duplicated centrosomes, followed by conversion to stable end-on attachment capable of generating force via depolymerization-coupled pulling. Chromosome congression begins and spindle assembly checkpoint proteins Mad1, Mad2, Bub1, BubR1 accumulate at unattached kinetochores to delay anaphase. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.