BUBR1BUB3

BUBR1BUB3 refers to the functional relationship between two spindle assembly checkpoint proteins, BubR1 and Bub3, and is not a distinct gene. In many studies, the term describes how these proteins form a complex that contributes to the surveillance of chromosome alignment during mitosis.

BubR1 (also known as BUB1B) is a kinase-like protein that participates in checkpoint signaling, while Bub3 is a WD40-repeat protein that binds BubR1 and other checkpoint components. Together, BubR1 and Bub3 help build the mitotic checkpoint complex (MCC), which also includes MAD2 and CDC20. The MCC inhibits the anaphase-promoting complex/cyclosome (APC/C), thereby delaying anaphase onset when kinetochores are unattached or not under proper tension.

Mechanistically, the BubR1–Bub3 interaction supports recruitment and stabilization of MAD2 and CDC20 at kinetochores, contributing to APC/C inhibition. When all chromosomes achieve correct bi-orientation and sufficient tension, the MCC is disassembled, releasing CDC20 and activating APC/C to drive the cell into anaphase. The BubR1–Bub3 module thus acts as a key regulatory node that prevents premature chromosome separation.

Evolutionarily, BubR1 and Bub3 are conserved across eukaryotes and are essential for accurate chromosome segregation in many organisms. Dysregulation or loss of function of these proteins can lead to chromosomal instability and aneuploidy. In humans, mutations in BUB1B, encoding BubR1, have been linked to mosaic variegated aneuploidy and an increased cancer risk in some contexts, highlighting the clinical relevance of SAC components.

See also: spindle assembly checkpoint, MCC, MAD2, CDC20, APC/C.