PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) inmitosis. Numerous roles for PICH have been proposed from protein depletion experiments,but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cellscauses chromosome structural abnormalities, and hypersensitivity to an inhibitor ofTopoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH-/- cells undergo sisterchromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localiseswith Topo II? on UFBs and at the ribosomal DNA locus, and the timely resolution of bothstructures depends on the ATPase activity of PICH. Purified PICH protein stronglystimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH-/- cellline exhibits chromosome instability and chromosome condensation and decatenationdefects similar to those of ICRF-193-treated cells. We propose that PICH and Topo IIcooperate to prevent chromosome missegregation events in mitosis.