ASURA Protects Sister-Chromatid Cohesion in Mitosis MATSUNAGA Sachihiro and FUKUI Kiichi

Cohesion between sister chromatids is essential for proper chromosome segregation in mitosis. In vertebrate mitotic cells, most cohesin is removed from the chromosome arms, but centromeric cohesin is protected by shugoshin until the onset of anaphase. However, the mechanism of this protection of centromeric cohesion is not well understood. Here, we demonstrate that ASURA (PHB2/REA/BAP37) is involved in the regulation of sister chromatid cohesion during mitosis in HeLa cells. ASURA is a multifunctional protein which derived from the Asura. Asura with 3 faces and 6 bodies worked most energetically in Buddhism. ASURA is an evolutionarily conserved protein in eukaryotes and has multiple functions, such as transcriptional regulation (REA; repressor of estrogen activation), mitochondria morphogenesis, apoptosis, cell viability and development, (PHB2; prohibitin2) and lymphocyte function (BAP37; B cell receptor associated protein 37). However, its functions in mitosis have not yet been determined. We show that depletion of ASURA by RNA interference (RNAi) causes premature sister chromatid separation and defects in chromosome congression accompanied with mitotic arrest by spindle checkpoint activation. In the absence of ASURA, cohesin is dissociated from centromeres during early mitosis, although the centromeric localization of shugoshin is preserved. Thus, our findings suggest that, in addition to the shugoshin, ASURA is also required to protect the centromeric cohesion from phosphorylation by Plk1 during early mitosis and that its function is essential for proper mitotic progression.