Reactome | Separation of Sister Chromatids

Separation of Sister Chromatids

Stable Identifier

R-HSA-2467813

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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While sister chromatids resolve in prometaphase, separating along chromosomal arms, the cohesion of sister centromeres persists until anaphase. At the anaphase onset, the anaphase promoting complex/cyclosome (APC/C) ubiquitinates PTTG1 (securin), targeting it for degradation (Hagting et al. 2002). PTTG1 acts as an inhibitor of ESPL1 (known as separin i.e. separase). Hence, PTTG1 removal initiated by APC/C, enables ESPL1 to become catalytically active (Zou et al. 1999, Waizenegger et al. 2002). ESPL1 undergoes autoleavage (Waizenegger et al. 2002) and also cleaves RAD21 subunit of centromeric cohesin (Hauf et al. 2001). RAD21 cleavage promotes dissociation of cohesin complexes from sister centromeres, leading to separation of sister chromatids. Subsequent movement of sister chromatids to opposite poles of the mitotic spindle segregates replicated chromosomes to two daughter cells (Waizenegger et al. 2000, Hauf et al. 2001, Waizenegger et al. 2002).

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
11081627	Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase Waizenegger, IC, Hauf, S, Meinke, A, Peters, JM	Cell	2000
12070128	Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1 Hagting, A, Den Elzen, N, Vodermaier, HC, Waizenegger, IC, Peters, JM, Pines, J	J Cell Biol	2002
12194817	Regulation of human separase by securin binding and autocleavage Waizenegger, I, Giménez-Abián, JF, Wernic, D, Peters, JM	Curr. Biol.	2002
10411507	Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis Zou, H, McGarry, TJ, Bernal, T, Kirschner, MW	Science	1999