PathwayStep4664 PathwayStep4670 PathwayStep4671 PathwayStep4666 PathwayStep4665 PathwayStep4668 PathwayStep4667 PathwayStep4669 Degradation of multiubiquitinated Securin Deacetylation of cleaved cohesin Separation of sister chromatids EPSL1 (Separin) cleaves centromeric cohesin Autocleavage of Separase Securin sequesters Separase Association of Securin with Cdc20:APC/C complex Ubiquitination of Securin by phospho-APC/C:Cdc20 complex Separation of Sister Chromatids Authored: Orlic-Milacic, M, 2012-10-02 Edited: Gillespie, ME, 2012-10-05 Edited: Matthews, L, 2012-10-05 Pubmed10411507 Pubmed11081627 Pubmed11509732 Pubmed12070128 Pubmed12194817 Reactome Database ID Release 432467813 Reactome, http://www.reactome.org ReactomeREACT_150471 Reviewed: Zhang, Nenggang, 2012-10-22 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).