Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis

Cytometry. Part a : the Journal of the International Society for Analytical Cytology
Akira KuroseZbigniew Darzynkiewicz

Abstract

DNA replication stress often induces DNA damage. The antitumor drug hydroxyurea (HU), a potent inhibitor of ribonucleotide reductase that halts DNA replication through its effects on cellular deoxynucleotide pools, was shown to damage DNA inducing double-strand breaks (DSBs). Aphidicolin (APH), an inhibitor of alpha-like DNA polymerases, was also reported to cause DNA damage, but the evidence for induction of DSBs by APH is not straightforward. Histone H2AX is phosphorylated on Ser 139 in response to DSBs and one of the protein kinases that phosphorylate H2AX is ataxia telangiectasia mutated (ATM); activation of ATM is through its phosphorylation of Ser 1981. The present study was undertaken to reveal whether H2AX is phosphorylated in cells exposed to HU or APH and whether its phosphorylation is mediated by ATM. HL-60 cells were treated in cultures with 0.1-5.0 mM HU or 1-4 muM APH for up to 5 h. Activation of ATM and H2AX phosphorylation was detected immunocytochemically using Ab specific to Ser1981-ATM or Ser 139-H2AX epitopes, respectively, concurrent with measurement of cellular DNA content. While exposure of cells to HU led to H2AX phosphorylation selectively during S phase and the cells progressing through the early porti...Continue Reading

References

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R A TobeyH A Crissman
Jan 1, 1991·Cytometry·B D HoffmanM Lalande
Jun 10, 1988·Nucleic Acids Research·L ArabshahiG Wright
May 16, 1984·Biochemical and Biophysical Research Communications·L BroxA Belch
Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·M B Kastan, D S Lim
Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Oct 24, 2001·The Journal of Biological Chemistry·I M Ward, J Chen
Sep 19, 2002·Radiation Research·Olga A SedelnikovaWilliam M Bonner
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Aug 5, 2003·Molecular and Cellular Biology·Kai RothkammMarkus Löbrich
Aug 26, 2003·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Morihito TakitaKohsuke Sasaki
Apr 2, 2004·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Xuan HuangZbigniew Darzynkiewicz
Jul 10, 2004·Cell·Christopher J Bakkenist, Michael B Kastan
Apr 23, 2005·Cell Cycle·Jirina BartkovaJiri Bartek
Jul 21, 2005·Molecular Biology of the Cell·Kirk J McManus, Michael J Hendzel
Aug 16, 2005·Cell Proliferation·Xuan HuangZbigniew Darzynkiewicz
Sep 13, 2005·Biochemical and Biophysical Research Communications·Yosuke IchijimaHirobumi Teraoka
Sep 27, 2005·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Akira KuroseZbigniew Darzynkiewicz

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Citations

Apr 21, 2011·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Fen ZhouRunming Jin
Nov 14, 2008·Nature Reviews. Cancer·William M BonnerYves Pommier
Jul 13, 2012·Molecular Biology of the Cell·Artem K VelichkoSergey V Razin
Jan 1, 2014·Plastic and Reconstructive Surgery·Justin R HubenakSteven J Kronowitz
Sep 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christophe E RedonYves Pommier
Oct 20, 2009·European Journal of Pharmacology·Zbigniew DarzynkiewiczDonald Wlodkowic
Apr 9, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Kazuo Ozawa
Jul 12, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Toshiki TanakaZbigniew Darzynkiewicz
Sep 20, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Nov 10, 2012·Critical Reviews in Clinical Laboratory Sciences·Zbigniew DarzynkiewiczDonald Wlodkowic
Jan 4, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Andrea Lisa HolmeShazib Pervaiz
Dec 17, 2009·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Aug 8, 2020·Frontiers in Cell and Developmental Biology·Naif Al-JomahRaj Patel
Mar 15, 2012·Biochemical Pharmacology·Robert A ForrestSuzanne M Cutts

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