BACKGROUND: Cohesin mediates sister chromatid cohesion by topologically 
entrapping sister DNA molecules inside its ring structure. Cohesin is loaded 
onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on 
the adenosine triphosphatase (ATPase) activity of cohesin's Smc1 and Smc3 
subunits. Subsequent cohesion establishment during DNA replication depends on 
Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which "locks" 
cohesin on DNA by inactivating the cohesin release factor Wapl.
RESULTS: Human cohesin ATPase mutants associate transiently with DNA in a manner 
that depends on the loading complex but cannot be stabilized on chromatin by 
depletion of Wapl. These mutants cannot be acetylated, fail to interact with 
sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the 
ATPase mutants is not a consequence of their transient association with DNA but 
is directly caused by their inability to hydrolyze ATP because acetylation of 
wild-type cohesin also depends on ATP hydrolysis.
CONCLUSIONS: Our data indicate that cohesion establishment involves the 
following steps. First, cohesin transiently associates with DNA in a manner that 
depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to 
entrapment of DNA and converts Smc3 into a state that can be acetylated. 
Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, 
and stabilization of cohesin on DNA. Our finding that cohesin's ATPase activity 
is required for both cohesin loading and Smc3 acetylation raises the possibility 
that cohesion establishment is directly coupled to the reaction in which cohesin 
entraps DNA.