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

• DOI: 10.1038/ncomms9962
• Publication Date: 2015-12-08T10:11:10Z
• Authors: Christian F. Nielsen; Diana Huttner; Anna H. Bizard; Seiki Hirano; Tian-Neng Li; Timea Palmai-Pallag; Victoria A. Bjerr...; Ying Liu; Erich A. Nigg; Lily Hui-Ching Wang; Ian D. Hickson
• Keywords: Blotting, Western; Mitosis; C700 Molecular Biology; Cell Cycle Proteins; 612; Chromatids; Article; Avian Proteins; Gene Knockout Techniques; 03 medical and health sciences; Antigens, Neoplasm; Cell Line, Tumor; Chromosomal Instability; Chromosome Segregation; Animals; Humans; Lymphocytes; Fluorescent Antibody Technique, Indirect; C440 Molecular Genetics; 0303 health sciences; C130 Cell Biology; DNA Helicases; Flow Cytometry; C420 Human Genetics; DNA-Binding Proteins; DNA Topoisomerases, Type II; Biophysics and Biochemistry; C700 Molecular Biology, Biophysics and Biochemistry; Chickens

AbstractPICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. 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 cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH−/− cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH−/− cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis.