Fission yeast has two members of the Shugoshin family, Sgo1 and Sgo2. Although Sgo1 has clearly been established as a protector of centromere cohesion in meiosis I, the roles of Sgo2 remain elusive. Here we show that Sgo2 is required to ensure proper chromosome biorientation upon recovery from a prolonged spindle checkpoint arrest. Consistent with this, Sgo2 is essential for maintaining the Passenger proteins on centromeres upon checkpoint activation. Interestingly, lack of Sgo2 has a more penetrant effect on the localization of Survivin than on the two other Passenger proteins INCENP and Aurora B, and the Survivin-INCENP complex but not the INCENP-Aurora B complex is destabilized in the absence of Sgo2. Finally we show that the conserved C-terminus of Sgo2 is crucial to maintain Sgo2 and Passenger proteins localization on centromeres upon prolonged checkpoint activation. Taken together, our results demonstrate that Sgo2 is important for chromosome biorientation and that it controls docking of the Passenger proteins on chromosomes in early mitotic cells.
INTRODUCTIONTo ensure the accuracy of chromosome segregation in mitosis, duplicated sister-chromatids must attach their kinetochores to microtubules emanating from opposite poles, a process referred to as chromosome biorientation. A single mal-orientated chromosome can be recognized by the spindle checkpoint that will block anaphase onset by inhibiting the activity of the anaphase-promoting complex (APC/C). Once all chromosomes are properly biorientated on the metaphase spindle, the spindle checkpoint is silenced and cells proceed through anaphase (for review, see Pinsky and Biggins, 2005).One of the best characterized roles of the kinase Aurora B is to correct defective kinetochore-microtubule attachment before anaphase onset and therefore ensure proper chromosome biorientation (Tanaka et al., 2002;Ditchfield et al., 2003;Hauf et al., 2003;Tanaka, 2005;Pinsky et al., 2006). Aurora B is also crucial for the recruitment of some spindle checkpoint components to kinetochores (Ditchfield et al., 2003;Vigneron et al., 2004). Thus Aurora B regulates both the physical connections of chromosomes onto the spindle and mitotic progression. When Aurora B activity is compromised, chromosomes mis-segregate massively, leading to aneuploidy (reviewed in Giet et al., 2005). Defective kinetochore-microtubules attachments accumulate in these cells and chromosomes never reach a proper metaphase plate (Hauf et al., 2003).Aurora B is one of the Chromosomal Passenger proteins, first identified in vertebrates as proteins sharing a complex and highly regulated localization pattern in mitosis (Earnshaw and Bernat, 1991). In particular they transfer abruptly from the inner-centromeres to the spindle midzone at the metaphase to anaphase transition. Each Chromosomal Passenger protein, Survivin, Borealin, TD60, INCENP, and Aurora B has long been recognized as major regulators of mitosis (see Vagnarelli and Earnshaw, 2004 for review). In fission yeast, homologues of only three of the Chromoso...