Imatinib inhibits inactivation of the ATM/ATR signaling pathway and recovery from adriamycin/doxorubicin-induced DNA damage checkpoint arrest

Cell Biology International
Mariko MoriiNaoto Yamaguchi

Abstract

The DNA damage checkpoint arrests cell cycle progression to allow time for DNA repair. After completion of DNA repair, checkpoint activation is terminated, and cell cycle progression is resumed in a process called checkpoint recovery. The activation of the checkpoint has been studied in depth, but little is known about recovery from the DNA damage checkpoint. Recently we showed that Src family kinases promote recovery from the G2 DNA damage checkpoint. Here we show that imatinib inhibits inactivation of ATM/ATR signaling pathway to suppress recovery from Adriamycin/doxorubicin-induced DNA damage checkpoint arrest. Imatinib and pazopanib, two distinct inhibitors of PDGFR/c-Kit family kinases, delayed recovery from checkpoint arrest and inhibited the subsequent S-G2-M transition after Adriamycin exposure. By contrast, imatinib and pazopanib did not delay the recovery from checkpoint arrest in the presence of an ATM/ATR inhibitor caffeine. Consistently, imatinib induced a persistent activation of ATR-Chk1 signaling. By the way, the maintenance of G2 checkpoint arrest is largely dependent on ATR-Chk1 signaling. However, unlike Src inhibition, imatinib did not delay the recovery from checkpoint arrest in the presence of an ATM inhib...Continue Reading

References

Feb 22, 2000·The Journal of Biological Chemistry·P R GravesH Piwnica-Worms
May 18, 2001·Nature·P Blume-Jensen, T Hunter
May 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Katia ScotlandiPiero Picci
Feb 5, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Iranzu GonzálezEnrique de Alava
Sep 3, 2004·Nature Reviews. Cancer·Nick J DibbClifford D Mol
Sep 8, 2004·Molecular Cell·Marcel A T M van VugtRené H Medema
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Jiri BartekJiri Lukas
Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
Dec 6, 2005·Nature Cell Biology·Ali JazayeriStephen P Jackson
Apr 14, 2006·Nature Reviews. Cancer·Charles Massie, Ian G Mills
Feb 17, 2007·Current Opinion in Cell Biology·Jiri Bartek, Jiri Lukas
Mar 31, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Seung-Mo HongEunsil Yu
Aug 28, 2007·Nature Biotechnology·Marcus BantscheffGerard Drewes
Sep 14, 2007·DNA Repair·Teresa M Calonge, Matthew J O'Connell
Jan 10, 2008·Nature Biotechnology·Mazen W KaramanPatrick P Zarrinkar
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Jul 11, 2008·Nature·Libor MacůrekRené H Medema
Sep 27, 2008·Experimental Cell Research·Kikuko IkedaNaoto Yamaguchi
Feb 28, 2009·Experimental Cell Research·Akinori TakahashiNaoto Yamaguchi
Aug 28, 2010·Cell Death and Differentiation·X WangB Li
Nov 1, 2011·Nature Biotechnology·Mindy I DavisPatrick P Zarrinkar
Dec 12, 2012·Journal of Cell Science·Kenichi IshibashiNaoto Yamaguchi
Mar 19, 2014·The Journal of Biological Chemistry·Yasunori FukumotoNaoto Yamaguchi
Jun 28, 2014·Biochemical and Biophysical Research Communications·Yasunori FukumotoNaoto Yamaguchi
Sep 1, 2014·Biochemical and Biophysical Research Communications·Yasunori FukumotoNaoto Yamaguchi

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Citations

Apr 8, 2020·Future Oncology·Sayantani RoychoudhuryNilesh Kumar Sharma
Dec 22, 2016·The Journal of Biological Chemistry·Mariko MoriiNaoto Yamaguchi
Jan 30, 2021·Scientific Reports·Mariko MoriiNaoto Yamaguchi
Feb 12, 2021·The Journal of Biological Chemistry·Trisiani AffandiMary E Reyland
Oct 14, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Guadalupe M VedoyaGabriela A Martín
Sep 15, 2021·Cell Biology and Toxicology·Andrea Ghelli Luserna Di RoràGiorgia Simonetti

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