The cohesin complex loads onto chromatin in telophase, but its association with chromatin remains transient, dynamic until the S-phase of the cell cycle, presumably because the cohesin-bound NIPBL:MAU2 (SCC2:SCC4) complex promotes chromatin loading, while cohesin-bound WAPAL promotes dissociation from chromatin. Stable binding of cohesin complexes to chromatin, measured by a mean residence time on chromatin, is triggered by DNA replication in S-phase (Gerlich et al. 2006), consistent with establishment of sister chromatid cohesion.
In S-phase, acetyltransferases ESCO1 and ESCO2 acetylate the SMC3 cohesin subunit (Hou and Zou 2005, Zhang et al. 2008, Nishiyama et al. 2010, Whelan et al. 2012). The acetylation of SMC3, in addition to DNA replication and the presence of PDS5 on cohesin, facilitates the recruitment of CDCA5 (Sororin) to cohesin complexes, an essential step in the establishment of sister chromatid cohesion in mammalian cells (Rankin et al. 2005, Nishiyama et al. 2010). CDCA5 (Sororin) displaces WAPAL from PDS5, thus preventing WAPAL to interfere with the establishment of sister chromatid cohesion (Nishiyama et al. 2010). The establishment and temporal regulation of sister chromatid cohesion is necessary for equal segregation of replicated chromosomes to daughter cells.