Cellular responses to the DNA strand-scission enediyne C-1027 can be independent of ATM, ATR, and DNA-PK kinases.

The Journal of Biological Chemistry
Jaroslaw Dziegielewski, T A Beerman

Abstract

The current paradigm based upon ionizing radiation (IR) studies states that cells deficient in either ataxia-telangiectasia-mutated kinase (ATM) or related phosphatidylinositol 3 (PI 3) -kinases (ATR and DNA-PK) are hypersensitive to DNA strand breaks because they are unable to rapidly activate downstream effectors such as p53. Here we have contrasted cell responses to IR and C-1027, a radiomimetic antibiotic that induces DNA strand breaks. At equal levels of DNA double strand breaks, cell lines with inactive ATM or other phosphatidylinositol 3-kinases displayed classical hypersensitivity to IR but not to C-1027. Moreover, phosphorylation of p53 Ser-15 induced by C-1027 was independent of ATM, ATR, or DNA-PK function. We have concluded that the model based on IR studies cannot always be directly applied to DNA damage induced by other strand-scission agents.

References

Apr 1, 1990·The Journal of Antibiotics·Y SugimotoY Yamada
Oct 1, 1985·Mutation Research·L R FergusonW T Jones
Dec 1, 1994·Seminars in Cell Biology·C W Anderson
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·A SuwaJ A Hardin
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·N A AbramovaR Li
Jul 1, 1997·The International Journal of Biochemistry & Cell Biology·S P Jackson
Apr 30, 1998·Current Opinion in Cell Biology·J Y Wang
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·J A WrightP Concannon
Sep 23, 1998·Genes & Development·K SakaguchiE Appella
Jan 23, 1999·Oncogene·C E Canman, D S Lim
Jan 30, 1999·Genes & Development·R S TibbettsR T Abraham
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·G C SmithS P Jackson
Oct 19, 1999·International Journal of Radiation Oncology, Biology, Physics·S J DiBiaseG Iliakis
Dec 23, 1999·The Journal of Biological Chemistry·S T KimM B Kastan
Dec 2, 2000·Nature·B B Zhou, S J Elledge
Feb 15, 2001·Biochemistry·J DziegielewskiT A Beerman
Mar 10, 2001·International Journal of Radiation Oncology, Biology, Physics·L LiR J Legerski
Mar 15, 2001·Current Opinion in Cell Biology·D Durocher, S P Jackson

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Citations

Jan 3, 2003·Mutation Research·Jun YangPenelope J Duerksen-Hughes
Aug 15, 2003·Organic Letters·Byungman KangSukbok Chang
Jan 17, 2009·Cancer Research·Terry A BeermanMary M McHugh
Jul 18, 2003·BMC Cell Biology·Georges NoëlVincent Favaudon
Nov 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Daniel R KennedyTerry A Beerman
Jan 26, 2010·Radiation Research·Jaroslaw DziegielewskiJanet E Baulch
Aug 24, 2006·Journal of Cellular Biochemistry·Jen-Sing LiuThomas Melendy
Jul 12, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Toshiki TanakaZbigniew Darzynkiewicz
Aug 17, 2004·World Journal of Gastroenterology : WJG·Yue-Xin LiangRong-Guang Shao
Jan 19, 2005·World Journal of Gastroenterology : WJG·You-Ping LiuChang-Xiao Liu
Sep 18, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Fei-Fei HanYong-Su Zhen
Oct 20, 2009·European Journal of Pharmacology·Zbigniew DarzynkiewiczDonald Wlodkowic

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