SUMOylation stabilizes sister kinetochore biorientation to allow timely anaphase

Abstract

During mitosis, sister chromatids attach to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension, which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore–microtubule attachments remains unclear. Here we show that SUMOylation dampens error correction to allow stable sister kinetochore biorientation and timely anaphase onset. The Siz1/Siz2 SUMO ligases modify the pericentromere-localized shugoshin (Sgo1) protein before its tension-dependent release from chromatin. Sgo1 SUMOylation reduces its binding to protein phosphatase 2A (PP2A), and weakening of this interaction is important for stable biorientation. Unstable biorientation in SUMO-deficient cells is associated with persistence of the chromosome passenger complex (CPC) at centromeres, and SUMOylation of CPC subunit Bir1 also contributes to timely anaphase onset. We propose that SUMOylation acts in a combinatorial manner to facilitate dismantling of the error correction machinery within pericentromeres and thereby sharpen the metaphase–anaphase transition.

Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore

“…As two further tests of the impact of the ctf3-2A allele on overall kinetochore assembly and its timing, we quantified the kinetochore recruitment of Sgo1-GFP and Scc2-GFP in dividing cells. Sgo1 dissociates from centromeres upon sister kinetochore biorientation in a process that depends on SUMO signaling ( Nerusheva et al, 2014 ; Su et al, 2021 ). We did not observe a defect in the pattern of Sgo1-GFP localization in the ctf3-2A –expressing cells ( Fig.…”

The importance of microtubule-dependent tension in accurate chromosome segregation

“…Even with multiple rounds of unnecessary error correction, these cells have significantly lower chromosome missegregation levels than those lacking Sgo1. Together the results suggest that SUMOylation of Sgo1 and the CPC component Bir1 work to decrease Sgo1 localization, and thus dampen Aurora B (Ipl1)-mediated error correction to selectively stabilize bioriented kinetochore-microtubule attachments and promote timely anaphase onset ( Su et al, 2021 ). More work is needed to understand how the tension status is transmitted to these downstream effectors.…”

“…While phosphorylation has been a widely investigated post-translational modification that mediates signalling at centromeres and kinetochores, SUMOylation of proteins has recently been found to also play a role. The SUMOylation status of Sgo1, a well-established tension-sensitive protein, influences the timing of anaphase onset ( Su et al, 2021 ). Sgo1 is recruited to the pericentromeric region during metaphase by phosphorylation of S121 on histone H2A ( Fernius and Hardwick, 2007 ); ( Yamagishi et al, 2010 ).…”

“…Sgo1 SUMOylation is needed to keep sister chromatids in a stable bioriented state. Metaphase arrested cells harbouring a mutation in the coiled-coil region of Sgo1 (sgo1-4R) that reduces SUMOylation display cycles of biorientation, loss of tension, detachment, then reattachment to become bioriented again ( Su et al, 2021 ). Even with multiple rounds of unnecessary error correction, these cells have significantly lower chromosome missegregation levels than those lacking Sgo1.…”

Coupling DNA Replication and Spindle Function in Saccharomyces cerevisiae

“…SUMO-dependent degradation of Sli15 and Bir1 is thought to diminish SAC activation and help cells escape SAC-induced arrest. Indeed, SUMOylation of Bir1 and pericentromeric shugoshin Sgo1 in unperturbed cells is thought to downregulate CPC activity at kinetochores in order to allow formation of stable MT-kinetochore connections, chromosome biorientation and timely entry into anaphase [ 56 ].…”