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.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Aug 2016 07:20
Deposited On:11 Aug 2016 07:20

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