Chromosome length influences replication-induced topological stress

Stress relief for chromosomes As the replication fork progresses along parental DNA during chromosome replication, there is a build-up of topological stress ahead of the polymerase. Current models propose that linear eukaryotic chromosomes are divided into topological domains, and that stress is relieved by the activity of a topoisomerase. Camilla Sjögren and colleagues find that replication stress is present throughout the chromosome, and that the relief of stress in longer chromosomes is facilitated by the activity of the cohesin/condensin-like Smc5/6 complex as well as by topoisomerase. They propose that the Smc5/6 complex prevent formation of topological tension ahead of the replication fork by promoting fork rotation, leading to the formation of sister chromatin intertwinings behind. During replication, topological stress builds ahead of the polymerase. Current models propose that linear eukaryotic chromosomes are divided into topological domains, and that stress is relieved by the activity of a topoisomerase. Here, it is found that replication stress seems to be present throughout the chromosome, rather than in domains, and that the relief of stress in longer chromosomes is facilitated by the activity of the cohesin/condensin-like Smc5/6 complex as well as by topoisomerase. They propose that the Smc5/6 complex prevent formation of topological tension ahead of the replication fork by promoting fork rotation, leading to the formation of sister chromatin intertwinings behind. During chromosome duplication the parental DNA molecule becomes overwound, or positively supercoiled, in the region ahead of the advancing replication fork. To allow fork progression, this superhelical tension has to be removed by topoisomerases, which operate by introducing transient DNA breaks 1 . Positive supercoiling can also be diminished if the advancing fork rotates along the DNA helix, but then sister chromatid intertwinings form in its wake 1 , 2 . Despite these insights it remains largely unknown how replication-induced superhelical stress is dealt with on linear, eukaryotic chromosomes. Here we show that this stress increases with the length of Saccharomyces cerevisiae chromosomes. This highlights the possibility that superhelical tension is handled on a chromosome scale and not only within topologically closed chromosomal domains as the current view predicts. We found that inhibition of type I topoisomerases leads to a late replication delay of longer, but not shorter,