title: PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis.
abstract: PICH 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.
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Nielsen
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Diana
authors.initials: D
authors.lastname: Huttner
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Anna H
authors.identifier: http://orcid.org/0000-0003-1858-3999
authors.initials: AH
authors.lastname: Bizard
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, OX3 9DS Oxford, UK.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hirano
authors.affiliation: Institute of Molecular and Cellular Biology &Department of Medical Science, National Tsing Hua University, 30013 Hsinchu, Taiwan.
authors.forename: Tian-Neng
authors.initials: TN
authors.lastname: Li
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, OX3 9DS Oxford, UK.
authors.forename: Timea
authors.identifier: http://orcid.org/0000-0002-7402-2144
authors.initials: T
authors.lastname: Palmai-Pallag
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Bjerregaard
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.affiliation: Institute of Molecular and Cellular Biology &Department of Medical Science, National Tsing Hua University, 30013 Hsinchu, Taiwan.|Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Lily Hui-Ching
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, OX3 9DS Oxford, UK.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hickson
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002645:Chickens; D002842:Chromatids / Q000378:metabolism*; D043171:Chromosomal Instability / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D055786:Gene Knockout Techniques; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D030161:Avian Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004265:DNA Helicases; C516980:ERCC6L protein, human; D004250:DNA Topoisomerases, Type II