DNA?topological?stress?inhibits?DNA?replication fork (RF) progression and contributes to?DNA?replication?stress. In Saccharomyces cerevisiae, we demonstrate that centromeric?DNA?and the rDNA array are especially vulnerable to?DNA?topological?stress?during replication. The activity of the SMC complexes?cohesin?and condensin are linked to both the generation and repair of?DNA?topological-stress-linked?damage?in these regions. At?cohesin-enriched centromeres,?cohesin?activity?causes?the accumulation of?DNA?damage, RF rotation, and pre-catenation, confirming that?cohesin-dependent?DNA?topological?stress?impacts on normal replication progression. In contrast, at the rDNA,?cohesin?an... More
DNA?topological?stress?inhibits?DNA?replication fork (RF) progression and contributes to?DNA?replication?stress. In Saccharomyces cerevisiae, we demonstrate that centromeric?DNA?and the rDNA array are especially vulnerable to?DNA?topological?stress?during replication. The activity of the SMC complexes?cohesin?and condensin are linked to both the generation and repair of?DNA?topological-stress-linked?damage?in these regions. At?cohesin-enriched centromeres,?cohesin?activity?causes?the accumulation of?DNA?damage, RF rotation, and pre-catenation, confirming that?cohesin-dependent?DNA?topological?stress?impacts on normal replication progression. In contrast, at the rDNA,?cohesin?and condensin activity inhibit the repair of?damage?caused by?DNA?topological?stress. We propose that, as well as generally acting to ensure faithful genetic inheritance, SMCs can disrupt genome stability by?trapping?DNA?topological?stress.
