Resolution of Sister Chromatid Cohesion

Stable Identifier
R-HSA-2500257
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
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).

Literature References
PubMed ID Title Journal Year
11509732 Cohesin cleavage by separase required for anaphase and cytokinesis in human cells

Hauf, S, Waizenegger, IC, Peters, JM

Science 2001
15723797 Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization

Kitajima, TS, Hauf, S, Ohsugi, M, Yamamoto, T, Watanabe, Y

Curr. Biol. 2005
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

Kitajima, TS, Sakuno, T, Ishiguro, K, Iemura, S, Natsume, T, Kawashima, SA, Watanabe, Y

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

Nishiyama, T, Ladurner, R, Schmitz, J, Kreidl, E, Schleiffer, A, Bhaskara, V, Bando, M, Shirahige, K, Hyman, AA, Mechtler, K, Peters, JM

Cell 2010
17112726 Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase

Gandhi, R, Gillespie, PJ, Hirano, T

Curr. Biol. 2006
14730319 The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis

Kitajima, TS, Kawashima, SA, Watanabe, Y

Nature 2004
15737063 Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2

Hauf, S, Roitinger, E, Koch, B, Dittrich, CM, Mechtler, K, Peters, JM

PLoS Biol 2005
17113138 Wapl controls the dynamic association of cohesin with chromatin

Kueng, S, Hegemann, B, Peters, BH, Lipp, JJ, Schleiffer, A, Mechtler, K, Peters, JM

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

Salic, A, Waters, JC, Mitchison, TJ

Cell 2004
21987589 Interaction of Sororin protein with polo-like kinase 1 mediates resolution of chromosomal arm cohesion

Zhang, N, Panigrahi, AK, Mao, Q, Pati, D

J. Biol. Chem. 2011
Participants
Participant Of
Orthologous Events
Authored
Reviewed