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

Nielsen, Christian F. and Huttner, Diana and Bizard, Anna H. and Hirano, Seiki and Li, Tian-Neng and Palmai-Pallag, Timea and Bjerregaard, Victoria A. and Liu, Ying and Nigg, Erich A. and Wang, Lily Hui-Ching and Hickson, Ian D. (2015) PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis. Nature Communications, 6 . p. 8962. ISSN 2041-1723

Full content URL: http://dx.doi.org/10.1038/ncomms9962

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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-localises
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.

Keywords:PICH, Topoisomerase II, chromosome missegregation, chromosome instability, genome maintenance, DNA catenation, UFBs, JCOpen
Subjects:C Biological Sciences > C440 Molecular Genetics
C Biological Sciences > C420 Human Genetics
C Biological Sciences > C130 Cell Biology
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:19561
Deposited On:22 Nov 2015 20:12

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