A New Mechanism for Boosting the Mitosis Efficiency

Eukaryotic cells use mitosis to accurately and efficiently separate their chromosomes into daughter cells. Kinetochores initially capture and associate laterally (side-on) with microtubules (MTs). Then the side-on attachment is converted to “end-on” attachment. The cells “sense” the status of the MT-kinetochore attachment through the spindle assembly checkpoint (SAC) proteins such as Bub3 and BubR1 because their kinetochore signals markedly decline or even disappear on end-on-attached kinetochores. Whether the checkpoint proteins and MTs could cooperate to facilitate the MT-kinetochore interactions, however, remains unclear.

In collaboration with Dr. ZHENG Yixian’s group in Carnegie Institution of Washington, PhD students JIANG Hao and HE Xiaonan, supervised by Dr. ZHU Xueliang at Institute of Biochemistry and Cell Biology, SIBS, CAS, identify a new mitotic regulator named BuGZ. They show that BuGZ is a spindle matrix protein capable of binding to Bub3. Knockdown of BuGZ by RNA interference destabilizes Bub3, resulting in mitotic arrest due to inefficient formation of end-on attachment. BuGZ also uses its MT-binding domain to enhance the loading of Bub3 onto kinetochores that have assumed side-on interactions with MTs. This enhanced Bub3 loading is required for proper chromosome alignment and mitotic progression. As Bub3 can sequentially recruit BubR1 and Cenp-E, whereas Cenp-E can stabilize side-on attachment and promote the conversion to end-on attachment, their results suggest that the cells use BuGZ to both stabilize Bub3 and promote the loading of Bub3, BubR1, and Cenp-E onto side-on-attached kinetochores for efficient chromosome alignment (Figure 1).

This work, entitled “A microtubule-associated zinc finger protein, BuGZ, regulates mitotic chromosome alignment by ensuring Bub3 stability and kinetochore targeting”, was published online in Developmental Cell on January 24, 2014. It was supported by grants from the NSFC, MOST, and CAS.