Safeguarding Genome Integrity: Polo-like kinase Cdc5 and phosphatase Cdc14 Orchestrate Topoisomerase II-Mediated Catenane Resolution in Mitosis

Resolution of sister chromatid intertwine in mitosis is vital for safeguarding genome integrity. While cohesin, condensin, the polo-like kinase Cdc5, and the phosphatase Cdc14 have all been implicated in this process, the underlying molecular mechanisms remain elusive. Our study unveils a coordination between spindle elongation and the timely resolution of DNA linkages orchestrated by Cdc14 and Cdc5. We show that Cdc14 and Cdc5 collaborate to facilitate the resolution of DNA catenanes, the predominant species of DNA intertwines in mitosis, by regulating Topoisomerase II (Top2) function, both through SUMOylation and via phosphorylation. Our findings contribute to unraveling a redundant mechanism wherein Cdc5 and Cdc14 work together to ensure the timely removal of all sources of cohesion between sister chromatids, thereby preserving the integrity of chromosome segregation and genome stability. Overall design: Calibrated Top2-PK ChIP-seq for TOP2 cdc20, TOP2-PK cdc20, TOP2-PK cdc5 cdc14 S. cerevisiase strains arrested in metaphase (cdc20) in presence or absence of nocodazole, in or in minianaphase (cdc4 cdc15). S. pombe is used as calibration genome