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PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis
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PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis
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Journal Article
PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis
2015
Overview
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.
During mitosis the translocase PICH binds to ultrafine bridges formed from DNA catenanes that are unresolved by topoisomerase II. In this study, the authors show that PICH stimulates toposiomerase II activity and that they cooperate to resolve these structures.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 14/34
/ 14/63
/ 82
/ 82/80
/ 82/83
/ Anaphase
/ Animals
/ Antigens, Neoplasm - metabolism
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Chickens
/ Chromosomal Instability - genetics
/ Chromosome Segregation - genetics
/ DNA
/ DNA topoisomerase (ATP-hydrolysing)
/ DNA Topoisomerases, Type II - metabolism
/ DNA-Binding Proteins - metabolism
/ Fluorescent Antibody Technique, Indirect
/ Humanities and Social Sciences
/ Humans
/ Mitosis
/ Proteins
/ Science
