Practice question

Centromere is specialized chromosomal domain that appears as primary constriction in metaphase chromosomes and functions as essential platform for kinetochore assembly linking chromosomes to spindle microtubules and providing tension sensor. Human centromeres built on megabases of alpha-satellite repeat DNA enriched with nucleosomes containing histone variant CENP-A replacing H3, deposited by chaperone HJURP in G1, epigenetically marking locus independent of sequence alone. CENP-A recruits constitutive centromere-associated network including CENP-C, CENP-I, CENP-H, CENP-T-W-S-X complex forming inner kinetochore bridging DNA to outer kinetochore KMN network composed of KNL1 scaffold, Mis12 complex, and Ndc80 complex that directly binds microtubule plus ends via calponin homology domains. This trilaminar structure translates microtubule dynamics into chromosome movement and recruits spindle assembly checkpoint proteins Mad1, Mad2, Bub1 until biorientation satisfied. Artificial chromosome assays show alpha-satellite plus CENP-B boxes required for stable inheritance, proving centromere function indispensable for segregation during mitosis and meiosis. 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.