Mitotic entry upon Topo II catalytic inhibition is controlled by Chk1 and Plk1.

The FEBS Journal
María ArroyoJ Alberto Marchal

Abstract

Catalytic inhibition of topoisomerase II during G2 phase delays onset of mitosis due to the activation of the so-called decatenation checkpoint. This checkpoint is less known compared with the extensively studied G2 DNA damage checkpoint and is partially compromised in many tumor cells. We recently identified MCPH1 as a key regulator that confers cells with the capacity to adapt to the decatenation checkpoint. In the present work, we have explored the contributions of checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1), in order to better understand the molecular basis of decatenation checkpoint. Our results demonstrate that Chk1 function is required to sustain the G2 arrest induced by catalytic inhibition of Topo II. Interestingly, Chk1 loss of function restores adaptation in cells lacking MCPH1. Furthermore, we demonstrate that Plk1 function is required to bypass the decatenation checkpoint arrest in cells following Chk1 inhibition. Taken together, our data suggest that MCPH1 is critical to allow checkpoint adaptation by counteracting Chk1-mediated inactivation of Plk1. Importantly, we also provide evidence that MCPH1 function is not required to allow recovery from this checkpoint, which lends support to the notion that ...Continue Reading

References

Dec 1, 1985·Molecular and Cellular Biology·G I EvanJ M Bishop
Nov 19, 1993·Cell·L L Sandell, V A Zakian
Feb 22, 2000·The Journal of Biological Chemistry·P R GravesH Piwnica-Worms
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·P B DemingW K Kaufmann
Jul 31, 2002·The Journal of Biological Chemistry·Paula B DemingWilliam K Kaufmann
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nobumoto WatanabeHiroyuki Osada
Jul 10, 2004·Current Biology : CB·Juan F Giménez-AbiánJan-Michael Peters
Sep 8, 2004·Molecular Cell·Marcel A T M van VugtRené H Medema
Jun 21, 2005·Nature Structural & Molecular Biology·Zhenkun LouJunjie Chen
Aug 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nobumoto WatanabeHiroyuki Osada
Jun 20, 2006·Nature Cell Biology·Gemma K AldertonMark O'Driscoll
Jan 11, 2007·British Journal of Cancer·M Damelin, T H Bestor
Feb 13, 2007·Current Biology : CB·Martin SteegmaierWolfgang J Rettig
Feb 13, 2007·Current Biology : CB·Péter LénártJan-Michael Peters
Feb 17, 2007·Current Opinion in Cell Biology·Jiri Bartek, Jiri Lukas
Mar 27, 2007·Oncogene·R G Syljuåsen
May 15, 2008·Developmental Cell·Mark PetronczkiJan-Michael Peters
Apr 15, 2009·The Journal of Cell Biology·Arne LindqvistRené H Medema
Jun 24, 2009·The Journal of Cell Biology·Alexandra TibeliusAlwin Krämer
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Jul 28, 2010·Oncogene·J A L BrownC G Morrison
Feb 18, 2011·Molecular Biology of the Cell·Tamara A PotapovaGary J Gorbsky
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Petra Langerak, Paul Russell
Jul 12, 2013·The Journal of Investigative Dermatology·Kelly BrooksBrian Gabrielli
Feb 25, 2014·European Journal of Cell Biology·Thejaswini Venkatesh, Padmanaban S Suresh
Apr 8, 2015·Chromosoma·M ArroyoJ A Marchal
Oct 17, 2015·Oncotarget·Claire F AspinallStephen S Taylor
Apr 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·María ArroyoJ Alberto Marchal

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.