Reactome | Resolution of Sister Chromatid Cohesion

Resolution of Sister Chromatid Cohesion

Stable Identifier

R-HSA-2500257

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, chromosome, chromosome, centromeric region

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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).

Literature References

PubMed ID	Title	Journal	Year
15723797	Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization Hauf, S, Watanabe, Y, Ohsugi, M, Yamamoto, T, Kitajima, TS	Curr. Biol.	2005
11509732	Cohesin cleavage by separase required for anaphase and cytokinesis in human cells Peters, JM, Hauf, S, Waizenegger, IC	Science	2001
19696148	Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1 Shintomi, K, Hirano, T	Genes Dev.	2009
16541025	Shugoshin collaborates with protein phosphatase 2A to protect cohesin Natsume, T, Ishiguro, K, Watanabe, Y, Kawashima, SA, Kitajima, TS, Iemura, S, Sakuno, T	Nature	2006
21878504	Regulation of sororin by Cdk1-mediated phosphorylation Dreier, MR, Bekier, ME, Taylor, WR	J. Cell. Sci.	2011
21111234	Sororin mediates sister chromatid cohesion by antagonizing Wapl Kreidl, E, Ladurner, R, Hyman, AA, Peters, JM, Bando, M, Mechtler, K, Bhaskara, V, Schleiffer, A, Schmitz, J, Nishiyama, T, Shirahige, K	Cell	2010
17112726	Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase Gandhi, R, Hirano, T, Gillespie, PJ	Curr. Biol.	2006
14730319	The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis Kawashima, SA, Watanabe, Y, Kitajima, TS	Nature	2004
15737063	Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2 Roitinger, E, Mechtler, K, Dittrich, CM, Peters, JM, Hauf, S, Koch, B	PLoS Biol	2005
17113138	Wapl controls the dynamic association of cohesin with chromatin Peters, BH, Hegemann, B, Peters, JM, Mechtler, K, Schleiffer, A, Kueng, S, Lipp, JJ	Cell	2006
9649503	Identification of Xenopus SMC protein complexes required for sister chromatid cohesion Losada, A, Hirano, M, Hirano, T	Genes Dev.	1998
15339662	Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis Mitchison, TJ, Waters, JC, Salic, A	Cell	2004
21987589	Interaction of Sororin protein with polo-like kinase 1 mediates resolution of chromosomal arm cohesion Pati, D, Mao, Q, Panigrahi, AK, Zhang, N	J. Biol. Chem.	2011