Frank Uhlmann

Establishment of sister chromatid cohesion. (A) Establishment of cohesion during DNA replication. Replication fork-associated Eco1 acetylates Smc3, which renders cohesin resistant to the destabilizing activity of Wapl, a prerequisite for enduring sister chromatid cohesion. How Wapl destabilizes cohesin, and what further impact it has on the establishment of cohesion, is not known. Several additional cohesion establishment factors are depicted at the replication fork. Their mechanism of action is unknown, but they could aid the passage of the replication fork through cohesin rings, potentially by coordinating lagging strand loop release with the encounter of cohesin. (B) Cohesion establishment in response to DNA breaks in G2. The ability of cohesin to link two of its binding sites might establish interactions between sister chromatids because of their proximity in G2. In response to DNA damage, Eco1 stabilizes these links by Scc1 acetylation, which might be aided by the recruitment of Eco1 to break sites and genome-wide Scc1 phosphorylation by the damage-activated Chk1 kinase. Ac, acetyl group; Chl, chromosome loss; Csm, chromosome segregation in meiosis; Ctf, chromosome transmission fidelity; Eco, establishment of cohesion; Fen, flap endonuclease; Mrc, mediator of the replication checkpoint; PCNA, proliferating cell nuclear antigen; RFC, replication factor C; Scc, sister chromatid cohesion; Smc, structural maintenance of chromosomes; Tof, topoisomerase-1-associated factor; Wapl, wings apart-like.

Comparison of Smc complexes and their possible modes of action on chromosomes. (A) Cartoon of the subunit composition of the bacterial Smc complex, its binding sites along the circular bacterial chromosome, and a proposal of how it might compact the chromosome by establishing links between neighbouring binding sites. The movement of bacterial replication products towards opposite cell poles initiates from the parS partitioning locus, which is enriched in Smc complexes. Additional binding sites along the chromosome arms correlate with highly expressed genes, such as rRNA (rrn) and tRNA (trn). (B) The eukaryotic condensin complex has a chromosomal association pattern reminiscent of the bacterial Smc complex. It is enriched at the centromere (CEN) and at highly transcribed loci along the chromosome arms, including rRNA, tRNA and ribosomal protein genes (RPS and RPL). Condensin may similarly promote chromosome compaction by establishing interactions between neighbouring binding sites. The enrichment around the centromere provides additional mechanical stability around this locus during chromosome segregation. (C) Cohesin associates with chromosomes at the same loci as condensin, but shows pronounced translocation on loading in response to transcription, perhaps because of its longer mean residence time on chromosomes. Cohesin also establishes interactions between neighbouring binding sites as part of transcriptional insulators but has specialized in establishing stable interactions between sister chromatids during DNA replication. Brn, barren; Pds, precocious dissociation of sister chromatids; rRNA, ribosmal RNA; Scc, sister chromatid cohesion; Scp, segregation and condensation protein; Smc, structural maintenance of chromosomes; tRNA, transfer RNA; Wapl, wings apart-like; Ycg, yeast CapG; Ycs, yeast condensin subunit.