The cohesin complex establishes sister chromatid cohesion during S phase. In 
metazoan cells, most if not all cohesin dissociates from chromatin during 
mitotic prophase, leading to the formation of metaphase chromosomes with two 
cytologically discernible chromatids. This process, known as sister chromatid 
resolution, is believed to be a prerequisite for synchronous separation of 
sister chromatids in subsequent anaphase. To dissect this process at a 
mechanistic level, we set up an in vitro system. Sister chromatid resolution is 
severely impaired upon depletion of Wapl from Xenopus egg extracts. Exogenously 
added human Wapl can rescue these defects and, remarkably, it can do so in a 
very short time window of early mitosis. A similar set of observations is made 
for Pds5, a factor implicated previously in the stabilization of interphase 
cohesion. Characteristic amino acid motifs (the FGF motifs) in Wapl coordinate 
its physical and functional interactions with Pds5 and cohesin subunits. We 
propose that Wapl and Pds5 directly modulate conformational changes of cohesin 
to make it competent for dissociation from chromatin during prophase. Evidence 
is also presented that Sgo1 plays a hitherto underappreciated role in 
stabilizing cohesin along chromosome arms, which is antagonized by the mitotic 
kinases polo-like kinsase (Plk1) and aurora B.