Poly(ADP-Ribose) polymerase-1 and DNA-dependent protein kinase have equivalent roles in double strand break repair following ionizing radiation

International Journal of Radiation Oncology, Biology, Physics
Jody MitchellNicola J Curtin

Abstract

Radiation-induced DNA double strand breaks (DSBs) are predominantly repaired by nonhomologous end joining (NHEJ), involving DNA-dependent protein kinase (DNA-PK). Poly(ADP-ribose) polymerase-1 (PARP-1), well characterized for its role in single strand break repair, may also facilitate DSB repair. We investigated the activation of these enzymes by differing DNA ends and their interaction in the cellular response to ionizing radiation (IR). The effect of PARP and DNA-PK inhibitors (KU-0058684 and NU7441) on repair of IR-induced DSBs was investigated in DNA-PK and PARP-1 proficient and deficient cells by measuring gammaH2AX foci and neutral comets. Complementary in vitro enzyme kinetics assays demonstrated the affinities of DNA-PK and PARP-1 for DSBs with varying DNA termini. DNA-PK and PARP-1 both promoted the fast phase of resolution of IR-induced DSBs in cells. Inactivation of both enzymes was not additive, suggesting that PARP-1 and DNA-PK cooperate within the same pathway to promote DSB repair. The affinities of the two enzymes for oligonucleotides with blunt, 3' GGG or 5' GGG overhanging termini were similar and overlapping (K(d)(app) = 2.6-6.4nM for DNA-PK; 1.7-4.5nM for PARP-1). DNA-PK showed a slightly greater affinity fo...Continue Reading

References

Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·J M de MurciaG de Murcia
Jul 1, 1997·The International Journal of Biochemistry & Cell Biology·S P Jackson
Jun 11, 1998·The Journal of Biological Chemistry·T RuscettiS R Peterson
Apr 24, 1999·Genes & Development·G C Smith, S P Jackson
Jul 10, 1999·The Journal of Biological Chemistry·S Galande, T Kohwi-Shigematsu
May 17, 2000·Critical Reviews in Eukaryotic Gene Expression·S Galande, T Kohwi-Shigematsu
Mar 10, 2001·Nature Genetics·S K MahadevaiahP S Burgoyne
Nov 9, 2001·The Journal of Biological Chemistry·Susanne Mårtensson, Ola Hammarsten
Jul 15, 2003·Journal of Biomolecular Screening·Krystyna J DillonNiall M B Martin
Feb 14, 2004·Journal of Cell Science·Michèle RouleauGuy G Poirier
Dec 14, 2004·Oncogene·Spencer J CollisAntony R Parker
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Boris KyselaPenny A Jeggo
Apr 20, 2005·Bioorganic & Medicinal Chemistry Letters·Vincent M LohAlan J Whittle
Nov 8, 2006·Nucleic Acids Research·Minli WangGeorge Iliakis
Feb 6, 2008·Nucleic Acids Research·Bustanur RosidiGeorge Iliakis
Dec 6, 2008·EMBO Reports·Kay E GurleyChristopher J Kemp
Feb 12, 2009·British Medical Bulletin·Anthony J Chalmers

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Citations

Aug 21, 2010·Cellular and Molecular Life Sciences : CMLS·Frédérique Mégnin-ChanetJanet Hall
Feb 2, 2013·Molecular Aspects of Medicine·Nicola J Curtin, Csaba Szabo
Apr 9, 2013·Trends in Biochemical Sciences·Alex PinesMartijn S Luijsterburg
Jan 10, 2012·Nucleic Acids Research·Laura SpagnoloLaurence H Pearl
Feb 2, 2012·The British Journal of Radiology·M I Koukourakis
Jan 26, 2016·Medicinal Research Reviews·Mohammad Zahid KamranVibha Tandon
Mar 6, 2010·Journal of Photochemistry and Photobiology. B, Biology·Karolin Kamel Abdul-Aziz, M J Tuorkey
Mar 31, 2015·Nucleic Acids Research·Pamela ReynoldsPeter O'Neill
Jul 2, 2011·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Somaira NowsheenEddy S Yang
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Xi WuJian-Ting Zhang
Mar 21, 2012·Carcinogenesis·Fabricio G SousaJenifer Saffi
May 21, 2013·British Journal of Pharmacology·N J Curtin
Sep 1, 2020·The Journal of Experimental Medicine·Angela HelfrichtHaico van Attikum

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