Separation of Sister Chromatids

Stable Identifier
R-HSA-2467813
Type
Pathway
Species
Homo sapiens
Compartment
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Summation

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
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
11509732 Cohesin cleavage by separase required for anaphase and cytokinesis in human cells

Hauf, S, Waizenegger, IC, Peters, JM

Science 2001
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
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