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

TY - JOUR

T1 - PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

AU - Nielsen, Christian Thomas Friberg

AU - Huttner, Diana

AU - Bizard, Anna H

AU - Hirano, Seiki

AU - Li, Tian-Neng

AU - Palmai-Pallag, Timea

AU - Bjerregaard, Victoria A

AU - Liu, Ying

AU - Nigg, Erich A

AU - Wang, Lily Hui-Ching

AU - Hickson, Ian D

PY - 2015/12/8

Y1 - 2015/12/8

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms9962

DO - 10.1038/ncomms9962

M3 - Journal article

C2 - 26643143

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8962

ER -