Resolution of Sister Chromatid Cohesion

Stable Identifier
Homo sapiens
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The resolution of sister chromatids in mitotic prometaphase involves removal of cohesin complexes from chromosomal arms, with preservation of cohesion at centromeres (Losada et al. 1998, Hauf et al. 2001, Hauf et al. 2005).

CDK1-mediated phosphorylation of cohesin-bound CDCA5 (Sororin) at threonine T159 provides a docking site for PLK1, enabling PLK1-mediated phosphorylation of cohesin subunits STAG2 (SA2) and RAD21 (Hauf et al. 2005, Dreier et al. 2011, Zhang et al. 2011). Further phosphorylation of CDCA5 by CDK1 results in dissociation of CDCA5 from cohesin complex, which restores the activity of WAPAL in removing STAG2-phosphorylated cohesin from chromosomal arms (Hauf et al. 2005, Gandhi et al. 2006, Kueng et al. 2006, Shintomi and Hirano 2006, Nishiyama et al. 2010, Zhang et al. 2011).

At centromeres, kinetochore proteins shugoshins (SGOL1 and SGOL2) enable PP2A-B56 (also a kinetochore constituent) to dephosphorylate the STAG2 subunit of centromeric cohesin. Dephosphorylation of STAG2 enables maintenance of centromeric cohesion, thus preventing separation of sister chromatids until anaphase (Salic et al. 2004, Kitajima et al. 2004, Kitajima et al. 2005, Kitajima et al. 2006).

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