Reactome: A Curated Pathway Database

Resolution of Sister Chromatid Cohesion (R-HSA-2500257)

Species Homo sapiens

Summation

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).

Locations in the PathwayBrowser
Additional Information
Compartment cytosol , chromosome , chromosome, centromeric region
Literature References
pubMedId Title Journal Year
9649503 Identification of Xenopus SMC protein complexes required for sister chromatid cohesion Genes Dev. 1998
11509732 Cohesin cleavage by separase required for anaphase and cytokinesis in human cells Science 2001
15737063 Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2 PLoS Biol 2005
15723797 Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization Curr. Biol. 2005
16541025 Shugoshin collaborates with protein phosphatase 2A to protect cohesin Nature 2006
14730319 The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis Nature 2004
21111234 Sororin mediates sister chromatid cohesion by antagonizing Wapl Cell 2010
21878504 Regulation of sororin by Cdk1-mediated phosphorylation J. Cell. Sci. 2011
21987589 Interaction of Sororin protein with polo-like kinase 1 mediates resolution of chromosomal arm cohesion J. Biol. Chem. 2011
17112726 Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase Curr. Biol. 2006
17113138 Wapl controls the dynamic association of cohesin with chromatin Cell 2006
19696148 Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1 Genes Dev. 2009
15339662 Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis Cell 2004