ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage

Current Biology : CB
M I AladjemG M Wahl

Abstract

Embryonic stem (ES) cells can contribute precursors to all adult cell lineages. Consequently, damage to ES cell genomes may cause serious developmental malfunctions. In somatic cells, cell-cycle checkpoints limit DNA damage by preventing DNA replication under conditions that may produce chromosomal aberrations. The tumor suppressor p53 is involved in such checkpoint controls and is also required to avoid a high rate of embryonic malformations. We characterized the cell-cycle and DNA-damage responses of ES cells to elucidate the mechanisms that prevent accumulation or transmission of damaged genomes during development. ES cells derived from wild-type mice did not undergo cell-cycle arrest in response to DNA damage or nucleotide depletion, although they synthesized abundant quantities of p53. The p53 protein in ES cells was cytoplasmic and translocated inefficiently to the nucleus upon nucleotide depletion. Expression of high levels of active p53 from an adenovirus vector could not trigger cell cycle arrest. Instead, ES cells that sustained DNA damage underwent p53-independent apoptosis. The antimetabolite-induced p53-dependent arrest response was restored in ES cells upon differentiation. Cell-cycle regulatory pathways in early ...Continue Reading

References

Apr 3, 1992·Cell·G I EvanD C Hancock
May 25, 1989·Nature·A W Murray, M W Kirschner
Nov 3, 1989·Science·L H Hartwell, T A Weinert
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·G C RiceR T Schimke
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·W LiJ R Bertino
Sep 1, 1995·Genes & Development·P SabbatiniE White
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·A AlmasanG M Wahl
Mar 3, 1995·Science·S M CrossB J Reid
Dec 16, 1994·Science·L H Hartwell, M B Kastan
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Wu, A J Levine
Jan 1, 1993·Methods in Enzymology·S J AbbondanzoC L Stewart
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M E PerryA J Levine
Sep 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·W K Kaufmann, D G Kaufman
Apr 1, 1993·Current Opinion in Cell Biology·T Hunt, M Kirschner
May 1, 1996·Nature Medicine·T NorimuraS Kondo
Aug 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M B Kastan
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·S N JonesA Bradley
Jan 1, 1997·Molecular and Cellular Biology·M H Kubbutat, K H Vousden
Feb 1, 1997·Current Opinion in Genetics & Development·R Hansen, M Oren

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Citations

Mar 15, 2006·Development Genes and Evolution·Leonardo RossiVittorio Gremigni
Feb 21, 2009·Apoptosis : an International Journal on Programmed Cell Death·Nikhil S ChariTimothy J McDonnell
Jul 4, 2012·Molecular Neurobiology·Susana SoláCecília M P Rodrigues
Mar 11, 2004·The International Journal of Biochemistry & Cell Biology·Robert Y L Tsai
Feb 14, 2002·Free Radical Biology & Medicine·Jonathan P CoeDavid J Harrison
Nov 7, 2000·Current Opinion in Cell Biology·N C Walworth
Sep 11, 2002·Trends in Cell Biology·Tom BurdonPierre Savatier
Dec 25, 2007·Cell Research·Meena ShrivastavJac A Nickoloff
Nov 26, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nick Fulcher, Robert Sablowski
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kyoung-Hwa LeeJing Huang
Oct 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Suzanne A HartfordJohn C Schimenti
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Amanda M GohDavid P Lane
May 11, 1999·DNA and Cell Biology·B S TzangY C Liu
Sep 10, 2009·Stem Cells and Development·Zuzana KoledovaVladimir Divoky
Jul 3, 2010·Stem Cells and Development·Zuzana KoledovaVladimir Divoky
Apr 16, 2013·Briefings in Functional Genomics·Richard P Halley-Stott, John B Gurdon
Jul 18, 2008·Human Molecular Genetics·Gayane Ambartsumyan, Amander T Clark
Dec 18, 2008·Human Reproduction·Marie-Justine GuerquinGabriel Livera
Jul 28, 2006·Nucleic Acids Research·Franck ToledoGeoffrey M Wahl
Mar 28, 2009·Journal of the Royal Society, Interface·Robert G ClydeJohn Crawford
Sep 10, 2010·Journal of the Royal Society, Interface·Emma StephensonDusko Ilic
Jun 17, 2010·Genes & Development·Courtney H CoschiFrederick A Dick
Jan 19, 2010·Development, Growth & Differentiation·Keiichi KatsumotoShoen Kume
Jun 8, 2002·Molecular and Cellular Biology·Anthony W I LoJohn P Murnane
Jul 30, 2004·Molecular and Cellular Biology·Kevin M HopkinsHoward B Lieberman
Jan 20, 2004·Molecular and Cellular Biology·Hayla K SlussStephen N Jones

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