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 -