Shugoshin enables tension-generating attachment of kinetochores by loading Aurora to centromeres

Abstract

Fission yeast shugoshin Sgo1 is meiosis specific and cooperates with protein phosphatase 2A to protect centromeric cohesin at meiosis I. The other shugoshin-like protein Sgo2, which requires the heterochromatin protein Swi6/HP1 for full viability, plays a crucial role for proper chromosome segregation at both mitosis and meiosis; however, the underlying mechanisms are totally elusive. We here demonstrate that, unlike Sgo1, Sgo2 is dispensable for centromeric protection of cohesin. Instead, Sgo2 interacts with Bir1/Survivin and promotes Aurora kinase complex localization to the pericentromeric region, to correct erroneous attachment of kinetochores and thereby enable tension-generating attachment. Forced localization of Bir1 to centromeres partly restored the defects of sgo2⌬. This newly identified interaction of shugoshin with Survivin is conserved between mitosis and meiosis and presumably across eukaryotes. We propose that ensuring bipolar attachment of kinetochores is the primary role of shugoshin and the role of cohesion protection might have codeveloped to facilitate this process.[Keywords: Shugoshin; spindle checkpoint; chromosome segregation; Aurora] Supplemental material is available at http://www.genesdev.org.

Shugoshin regulates cohesion by driving relocalization of PP2A in Xenopus extracts

“…The role of Sgo in the regulation of mitotic cohesion has been addressed in a number of recent studies, mainly in yeast and human cells McGuinness et al 2005;Vaur et al 2005;Kitajima et al 2006;Tang et al 2006;Kawashima et al 2007;Vanoosthuyse et al 2007;Lee et al 2008). However, this is the first time that the Xenopus egg cell free system, in which vertebrate cohesin was initially characterized, is used.…”

“…c One-μl aliquots of each depleted extract were analyzed by immunoblotting and compared with a mock-depleted extract to estimate the extent of depletion. Bars, 10 μm components (Kawashima et al 2007;Vanoosthuyse et al 2007;Yu and Koshland 2007). The interdependence of Aurora B and Sgo localization at centromeres remains to be investigated in detail, but it is likely to underlie the role of both proteins as sensors of tension across the sister kinetochores (Goulding and Earnshaw 2005).…”

“…The interdependence of Aurora B and Sgo localization at centromeres remains to be investigated in detail, but it is likely to underlie the role of both proteins as sensors of tension across the sister kinetochores (Goulding and Earnshaw 2005). This task appears to be more specific of Sgo2 in human and fission yeast (Kawashima et al 2007). We suspect that a single Sgo were analyzed by immunoblotting with Sgo and PP2A antibodies.…”

Detection and Correction of Merotelic Kinetochore Orientation by Aurora B and its Partners

“…67,68 Studies in fission yeast have also shown that Sgo2 interacts with and promotes the centromeric localization of INCENP/ Survivin. 69,70 It is less clear if the centromeric localization of Aurora kinase is also regulated by Sgo2, although it could do so indirectly via INCENP. Finally, in mammalian cells Sgo2 also seems to promote MCAK localization at the centromere and cells depleted of Sgo2 exhibit erroneous kinetochore-microtubule attachments and high rates of chromosome mis-segregation in anaphase.…”

Molecular insights into mechanisms regulating faithful chromosome separation in female meiosis

“…199 In Schizosaccharomyces pombe, Shugoshin2 interacts with Bir1/Survivin and promotes Aurora kinase complex localization to the pericentromeric region, to correct erroneous attachment of kinetochores, thereby enabling tension-generating attachment. 200 Thus, Shugoshin2 might also be a component of the tension-sensing machinery. 201 The understanding of Shugoshin function gives new insights on spindle checkpoint and chromosome separation.…”