Sister chromatids are held together during mitosis and meiosis by the ring-like protein cohesin. The establishment of cohesion is a complex process that appears to involve loading of cohesin onto DNA, along with other events. The details are obscure. Kim Nasmyth and co-workers have therefore sought to define key proteins that are involved. Analysing various mutant strains and employing suppressor screens, they show that five budding yeast proteins are required for efficient mitotic cohesion: the helicase Chl1p, Ctf4p and the proteins that together make up the specialized replication factor RF-CDcc1/Ctf18/Ctf8 (see p. 3547). They then place CHI1 under the control of an inducible promoter and show that the helicase acts during S phase, when cohesion is established. The authors go on to demonstrate that Chl1p, Ctf4p and RF-C are even more critical at meiosis: if one is absent, there is widespread chromosome mis-segregation at meiosis II. Nasmyth and co-workers conclude that the five proteins are important for establishing cohesion at DNA replication forks in S phase. They suggest that the increased sensitivity of meiosis II to weakened cohesion reflects the fact that cohesion is limited to centromeres at this division.