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

Nat Commun. 2015 Dec 8;6:8962. doi: 10.1038/ncomms9962.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism*
  • Avian Proteins / genetics*
  • Avian Proteins / metabolism
  • Blotting, Western
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Chickens
  • Chromatids / metabolism*
  • Chromosomal Instability / genetics
  • Chromosome Segregation / genetics*
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Gene Knockout Techniques
  • Humans
  • Lymphocytes / metabolism
  • Mitosis / genetics*

Substances

  • Antigens, Neoplasm
  • Avian Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • DNA Helicases
  • ERCC6L protein, human
  • DNA Topoisomerases, Type II