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.
Bibliographical noteFunding Information:
We would like to thank Dr Ashish Jain for supplying the materials, Si-Hyun Lee for providing excellent technical assistance and the Samsung Biomedical Research Institute for supplying the equipment, technical assistance and financial support. This study was supported by a National Research Foundation grant funded by the Korea government (MEST) (2011-0030833 and 2012-R1A1A2041656) and a grant from the National R and D program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1120220).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)