Hyun-Soo Kim1, Se-Hyuk Kim1, Hye-Young Park1, Janet Lee1, Jong Hyuk Yoon2, Sunkyu Choi2, Sung Ho Ryu2, Ho Lee3, Hyun-Soo Cho4 & Chang-Woo Lee1,5
1 Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Republic of Korea. 2 Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbook 790-784, Republic of Korea. 3 Research Institute, National Cancer Center, Goyang, Gyeonggi 411-764, Republic of Korea. 4 Department of Biology, Yonsei University, Seoul 120-749, Republic of Korea. 5 Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea.
Correspondence to: Chang-Woo Lee
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.