SUMOylation stabilizes sister kinetochore biorientation to allow timely anaphase

Su, X.B, Wang, M., Schaffner, C., Nerusheva, O.O., Clift, D., Spanos, C., Kelly, D.A., Tatham, M., Wallek, A., Wu, Y., Rappsilber, J., Jeyaprakash, A.A., Storchova, Z., Hay, R.T., and Marston, A.L.

Journal of Cell Biology (2021) 220 (7): e202005130

The proper attachment of sister chromatids to microtubules from opposite poles in mitosis is monitored by an assembly of pericentromeric signalling proteins. Su et al. show that SUMOylation regulates the signalling hub to allow timely chromosome segregation.

Summary of Paper by Lori Koch

To be inherited, chromosomes need to attach to fibres called microtubules that will pull them into the new cell. Ideally, each chromosome should attach to microtubules from the two opposite ends of the dividing cell. During this process, the protein Sgo1 brings the kinase Aurora B and the phosphatase PP2A to the place on the chromosome where the microtubule binds, the centromere, and together they ensure that proper attachments are made. In their recent study published in the Journal of Cell Biology, scientists in the Marston lab led by Xue Bessie Su discovered that the Sgo1 protein is modified by SUMOylation and this is important for making bioriented attachments. After previously finding that excess Sgo1 delays cell division in budding yeast, they performed a genetic screen to identify genes that could rescue cell growth in that condition if they were over-expressed. This identified the SUMO ligase Siz2 and they determined that Sgo1 protein itself is SUMOylated at multiple positions. Next, they found that preventing SUMOylation of Sgo1 increased the frequency of futile cycles of attachment and re-attachment of chromosomes. Consistent with this, there was elevated Aurora B kinase at centromeres, indicating that error-correction activity was increased. In vitro experiments showed that the interaction of Sgo1 with PP2A phosphatase was lost in cells lacking SUMOylation (siz1∆ siz2∆), suggesting that Aurora B phosphorylation may not be properly removed by opposing phosphatase in the absence of SUMOylation. Intriguingly, the scientists found that the protein Bir1, which regulates Aurora B, was also SUMOylated and that preventing SUMOylation of Sgo1 and Bir1 together delayed chromosome segregation similarly to the siz1∆ siz2∆ SUMOylation enzyme mutant. Together, the work uncovers that SUMOylation regulates the accuracy and timing of chromosome segregation during cell division.

 

Journal Link:

https://rupress.org/jcb/article/220/7/e202005130/212041/SUMOylation-stabilizes-sister-kinetochore

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