PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26643143.
- Also identified by DOI 10.1038/ncomms9962 and PMC identifier 4686863.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Antigens, Neoplasm
- Avian Proteins
- Cell Cycle Proteins
- Chromatids
- Chromosome Segregation
- DNA Helicases
- DNA Topoisomerases, Type II
- DNA-Binding Proteins
- Mitosis