Depletion of BubR1 promotes premature centrosomal localization of cyclin B₁ and accelerates mitotic entry

The role of BubR1 has been established mainly in mitosis as an essential mitotic checkpoint protein although it is expressed throughout the cell cycle. To explore a possible role of BubR1 in regulating the G₂ phase of cell cycle, we have employed siRNA-mediated hBubR1 knockdown in HeLa cells. Here, we demonstrate that reducing BubR1 levels during the G₂ phase causes accelerated mitotic entry. As expected, BubR1 depletion leads to degradation of cyclin B₁ in the G₂ phase. Intriguingly, cyclin B₁ is prematurely targeted to centrosomes appearing at early G₂ phase in BubR1-depleted cells despite its low levels. This is in contrast to control cells where cyclin B₁ appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G₂ is aberrantly high in BubR1-depleted cells. Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B₁ probably leading to premature mitotic entry. This study is the first to suggest a role of hBubR1 in controlling centrosome targeting of cyclin B₁ and timing of mitotic entry.