NIH R01 · 2025
Control of Chromosome Segregation by DNA Topoisomerase II
Title: Control of Chromosome Segregation by DNA Topoisomerase II. Abstract Chromosome segregation errors result in aneuploidy, which causes birth defects and cancer. We have defined a new mitotic Topo II-responsive control (TRC) that delays the cell cycle when Topo II activity is insufficient for accurate chromosome segregation. This TRC mechanism is conserved from yeast to human cells but has not been extensively studied. Activation of the TRC is triggered by stalling of the strand passage reaction of Topo II, when the enzyme becomes trapped on DNA in the Closed Clamp structural conformation. TRC activation requires two distinct modules within the catalytically inert C-terminal domain of…
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