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Accurate chromosome segregation requires that all pairs of sister chromatids become appropriately atttached to mitotic spindles before the onset of anaphase. Cell cycle checkpoints monitor kinetochore-microtubule interactions, so that cell cycle progression can be delayed until proper chromosome attachments are formed. In yeast, Bub1-3 genes are required for proper mitotic delay in response to unattached kinetochores. In mammals, the homologues to yeast Bub1 and Bub3 form a complex that binds kinetochores and has protein kinase activity. BUBR1 is a bub-related kinase homologous to Bub1 and MAD3. BUBR1 contains a nuclear localization signal and two highly conserved domains CD1 and CD2. CD1 is in the N-terminal region and is invoved in kinetochore localization, while CD2 is in the C-terminal region and is involved in kinase activity. BUBR1 is hyperphosphorylated during spindle checkpoint activation, and interacts with p55CDC and APC during spindle checkpoint function. In colorectal cancers, the BUBR1 gene has structural abnormalities that suggest BUBR1 is a tumor suppressor gene. Thus, BUBR1 may be a critical spindle checkpoint kinase and disruption of its function may be related to tumor formation.Immunofluorescence, Western Blotting
