Sister acts ‐ coordinating DNA replication & cohesion establishment

Abstract

The ring‐shaped cohesin complex links sister chromatids and plays crucial roles in homologous recombination and mitotic chromosome segregation. In cycling cells, cohesin's ability to generate such linkages is restricted to S phase and depends on so‐called establishment factors that are intimately connected to DNA replication. Paramount among these are the Eco1‐related family of acetyltransferases. By applying high‐resolution microscopy, somatic cell gene‐targeting, and next‐generation sequencing approaches, we have begun to delineate how human Eco1 orthologs are targeted to chromosomes, how their acetyltransferase activity is coupled to cell cycle progression, and how their acetylation of cohesin's Smc3 subunit triggers cohesion establishment.. Our data suggest a model whereby Smc3 acetylation regulates a ‘gate’ within cohesin that otherwise interferes with DNA replication fork passage, and whose closure is crucial for cohesin's stable interaction with replicated DNA molecules.