Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion

Hyun-Soo Kim, Se-Hyuk Kim, Hye-Young Park, Janet Lee, Jong Hyuk Yoon, Sunkyu Choi, Sung Ho Ryu, Ho Lee, Hyun-Soo Cho and Chang-Woo Lee ()
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Hyun-Soo Kim: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Se-Hyuk Kim: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Hye-Young Park: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Janet Lee: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Jong Hyuk Yoon: Pohang University of Science and Technology
Sunkyu Choi: Pohang University of Science and Technology
Sung Ho Ryu: Pohang University of Science and Technology
Ho Lee: Research Institute, National Cancer Center
Hyun-Soo Cho: Yonsei University
Chang-Woo Lee: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine

Nature Communications, 2013, vol. 4, issue 1, 1-14

Abstract: Abstract Cohesins establish cohesion between replicated sister chromatids and are maintained as a multiprotein complex on chromosome arms until they are phosphorylated by mitotic kinases, such as Aurora B and Plk1. However, the mechanics of how the phosphorylation and dephosphorylation of cohesin subunits by kinases and phosphatases, respectively, leads to the dissociation of the cohesin complex from chromosomes remain unclear. Here we report that Aurora B kinase directly interacts with and phosphorylates Ssu72, a new cohesin-binding phosphatase, at Ser 19 in vitro and in vivo. The Aurora B-mediated phosphorylation of Ssu72 causes the structural modification of Ssu72 protein, downregulates phosphatase activity and triggers the ubiquitin-dependent degradation of Ssu72. Overexpression of the Aurora B-mediated phosphomimetic mutant of Ssu72 prevents maintainance chromosome arm cohesion. These results provide evidence that Aurora B kinase directly targets Ssu72 phosphatase for regulation of sister chromatid cohesion during early mitosis.

Date: 2013
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DOI: 10.1038/ncomms3631

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