BUBR1

BUBR1 is an essential spindle assembly checkpoint protein that prevents premature anaphase onset and supports chromosome alignment and kinetochore-microtubule attachment^[1]. Mechanistically, BUBR1 inhibits APC/C^Cdc20 through its N-terminal Cdc20-binding KEN-box region, allowing cyclin B accumulation before mitotic entry^[2]. At kinetochores, BUBR1 links mitotic checkpoint signaling with chromosome-spindle attachment control and regulates CENP-A/Aurora kinase-associated attachment stability^[3]. In human cells, BUBR1/BUB3 exists in functionally distinct kinetochore pools: a Bub1-dependent pool supports chromosome alignment, whereas KNL1-MELT binding strengthens checkpoint-complex incorporation^[4]. Compared with Bub1, Bub1 is required for kinetochore localization of BUBR1, CENP-E, CENP-F, and Mad2, while BUBR1 is not required for kinetochore localization of Bub1 in human somatic cells^[5]. In disease models, reduced BUBR1 causes progressive aneuploidy, senescence, infertility, and progeroid phenotypes in mice, whereas sustained high-level BUBR1 expression preserves genomic integrity and reduces tumorigenesis^[6][7]. For experimental applications, bubristatin acts as a selective BUBR1 kinase antagonist and helps dissect BUBR1-CENP-E control of end-on microtubule capture^[8].