Sister chromatid cohesion (SCC), efficient DNA repair, and the regulation of 
some metazoan genes require the association of cohesins with chromosomes. 
Cohesins are deposited by a conserved heterodimeric loading complex composed of 
the Scc2 and Scc4 proteins in Saccharomyces cerevisiae, but how the Scc2/Scc4 
deposition complex regulates the spatiotemporal association of cohesin with 
chromosomes is not understood. We examined Scc2 chromatin association during the 
cell division cycle and found that the affinity of Scc2 for chromatin increases 
biphasically during the cell cycle, increasing first transiently in late G1 
phase and then again later in G2/M. Inactivation of Scc2 following DNA 
replication reduces cellular viability, suggesting that this post S-phase 
increase in Scc2 chromatin binding affinity is biologically relevant. 
Interestingly, high and low Scc2 chromatin binding levels correlate strongly 
with the presence of full-length or amino-terminally cleaved forms of Scc2, 
respectively, and the appearance of the cleaved Scc2 species is promoted in 
vitro either by treatment with specific cell cycle-staged cellular extracts or 
by dephosphorylation. Importantly, Scc2 cleavage eliminates Scc2-Scc4 physical 
interactions, and an scc2 truncation mutant that mimics in vivo Scc2 cleavage is 
defective for cohesin deposition. These observations suggest a previously 
unidentified mechanism for the spatiotemporal regulation of cohesin association 
with chromosomes through cell cycle regulation of Scc2 cohesin deposition 
activity by Scc2 dephosphorylation and cleavage.