Figure 2.

Building cohesion at the replication fork. At S-phase onset, replication forks encounter cohesin rings that are unacetylated and tightly bound to Wapl and Pds5, which antagonize cohesion establishment and replication fork progression. Through recruitment and activation of Eco1-related acetyltransferases, replication forks modify cohesin's Smc3 subunit to weaken its interaction with the Wapl–Pds5 complex. This may put cohesin in an “open” conformation that allows the replication fork to progress while trapping the nascent sister chromatids inside the ring. Alternatively, it is possible that cohesin rings are displaced by advancing replication forks, but then are subjected to a second round of loading behind the fork. However generated, entrapment of the nascent sister DNAs is likely to enhance fork stability by enabling homology-dependent pathways of fork repair and restart. Further discussion of these points can be found in the text.