Practice question

Spindle assembly checkpoint, also termed mitotic checkpoint, monitors mechanical and attachment state of chromosomes to ensure faithful segregation. Key parameter sensed is not DNA sequence integrity but physical connection between centromeric region, specifically kinetochore proteinaceous plaque assembled on centromeric chromatin, and dynamic microtubule plus ends emanating from spindle poles. Unattached kinetochores catalyze formation of diffusible inhibitor MCC that blocks APC/C-Cdc20, delaying anaphase until all sister pairs are bi-oriented with kinetochores attached to opposite poles and under tension from depolymerizing microtubules exerting pulling forces. Attachment is detected through Mps1 kinase sensing Ndc80-microtubule engagement and through tension-dependent dephosphorylation by PP1 phosphatase recruited to KNL1. DNA damage repair is surveyed by ATM/ATR kinases acting in interphase, G1-S transition is controlled by Rb-E2F pathway integrating growth signals, centrosome duplication is licensed by Plk4 and separase. Therefore SAC specifically ensures every chromosome is properly hooked to spindle apparatus, preventing chromosome loss or gain that underlies aneuploidy, tumor evolution, and developmental disorders when checkpoint fails.