Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC

Abad, M.A., Gupta, T., Hadders, M.A., Meppelink, A., Wopken, J.P., Blackburn, E., Zou, J., Gireesh, A., Buzuk, L., Kelly, D.A., McHugh, T., Rappsilber, J., Lens, S.M.A., and Jeyaprakash, A.A.

Journal of Cell Biology (2022) 221(8): e202108156


Abad and Gupta et al reveal the molecular basis for the interaction between the CPC and Sgo1, two essential regulators of chromosome segregation. Their work provides a rationale for the kinetochore-proximal recruitment of the CPC and highlights its requirement for high fidelity chromosome segregation. 

Summary of Paper by Lori Koch

Chromosome segregation is one of the most fundamental processes of all of life. New cells must inherit all of the chromosomes required for life in order to survive and reproduce properly. During cell division, the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP and Aurora B) monitors whether chromosomes are ready to be segregated and prevent progression until the right time. Shugoshin (Sgo1) is another protein important for chromosome segregation and previous studies have reported that Sgo1 binding to the centre of chromosomes, at a region called the centromere, is also required to localize CPC proteins to the same position. In their recent study published in the Journal of Cell Biology, scientists in the JP lab led by Alba Abad and Tanmay Gupta determined precise binding domains of the Sgo1-CPC interaction and demonstrated that these binding interfaces are essential for proper localization of CPC to the centromere in human cells. They purified CPC and Sgo1 proteins and using size-exclusion chromatography (SEC) and isothermal calorimetry (ITC), determined that they formed a stable complex in vitro (outside of cells). Using cross-linking mass spectrometry and crystallographic structure data from their previous studies, they observed interactions between the N-terminal coiled-coil of Sgo1 (amino acids 1-130) and the CPC, as well as interactions between an unstructured region of Sgo1 (amino acids 130-280) and the CPC. Using a LacO-LacI tethering system in cells, they showed that both domains of Sgo1 were able to recruit Borealin to the site of Sgo1 tethering in human cells. By making mutations in the Sgo1 coiled-coil (1-130) as well as the unstructured region (130-280) in human cells, they showed that both of these domains of Sgo1 are required for full localization of the CPC to the centromere in human cells. 

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