Mitotic molecular braking prevents DNA damage in anaphase

Abstract

During mitosis, duplicated sister chromatids are sorted into opposite poles of a dividing mother cell. In all eukaryotic cells, the speed at which sister chromatids are separated during anaphase, the final phase of mitosis, is limited by targeted regulatory mechanisms. However, the cellular consequence of exceeding this speed limit is unknown. In this study, we used budding yeast to investigate the consequences of exceeding the anaphase speed limit. Here, we discovered that, in budding yeast, a rapid rate of anaphase spindle elongation led to unresolved DNA catenations in anaphase, leading to DNA damage and nuclear division failure. A topoisomerase mutation with critically impaired DNA decatenation phenocopied these defects, while pre-anaphase pauses to facilitate decatenation rescued the DNA damage phenotype in the fast-anaphase mutants. Thus, our results describe a novel and essential genome protective pathway in which anaphase chromosome separation is maintained at a slow speed to allow for proper decatenation of DNA, thereby protecting genome stability. Budding yeast was used to investigate the consequences of exceeding the anaphase speed limit during mitosis, revealing that a rapid rate of anaphase spindle elongation led to DNA damage and nuclear division failure.