20 research outputs found
PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis
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-localises
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