This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Wang, Y. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Wang, Y.

ATR Affecting Cell Radiosensitivity Is Dependent on Homologous Recombination Repair but Independent of Nonhomologous End Joining

¹ Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; ² Laboratory of Molecular and Cellular Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts; and ³ Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany

ATR is one of the most important checkpoint proteins in mammalian cells responding to DNA damage. Cells defective in normal ATR activity are sensitive to ionizing radiation (IR). The mechanism by which ATR protects the cells from IR-induced killing remains unclear. DNA double-strand breaks (DSBs) induced by IR are critical lesions for cell survival. Two major DNA DSB repair pathways exist in mammalian cells: homologous recombination repair (HRR) and nonhomologous end joining (NHEJ). We show that the doxycycline (dox)-induced ATR kinase dead (ATRkd) cells have the similar inductions and rejoining rates of DNA DSBs compared with cells without dox induction, although the dox-induced ATRkd cells are more sensitive to IR and have the deficient S and G₂ checkpoints. We also show that the dox-induced ATRkd cells have a lower HRR efficiency compared with the cells without dox induction. These results indicate that the effects of ATR on cell radiosensitivity are independent of NHEJ but are linked to HRR that may be affected by the deficient S and G₂ checkpoints.

This article has been cited by other articles:

				K. A. Lewis, K. K. Lilly, E. A. Reynolds, W. P. Sullivan, S. H. Kaufmann, and W. A. Cliby Ataxia telangiectasia and rad3-related kinase contributes to cell cycle arrest and survival after cisplatin but not oxaliplatin Mol. Cancer Ther., April 1, 2009; 8(4): 855 - 863. [Abstract] [Full Text] [PDF]

				R. A. Chanoux, B. Yin, K. A. Urtishak, A. Asare, C. H. Bassing, and E. J. Brown ATR and H2AX Cooperate in Maintaining Genome Stability under Replication Stress J. Biol. Chem., February 27, 2009; 284(9): 5994 - 6003. [Abstract] [Full Text] [PDF]

				L. I. Toledo, M. Murga, P. Gutierrez-Martinez, R. Soria, and O. Fernandez-Capetillo ATR signaling can drive cells into senescence in the absence of DNA breaks Genes & Dev., February 1, 2008; 22(3): 297 - 302. [Abstract] [Full Text] [PDF]

				M. Murga, I. Jaco, Y. Fan, R. Soria, B. Martinez-Pastor, M. Cuadrado, S.-M. Yang, M. A. Blasco, A. I. Skoultchi, and O. Fernandez-Capetillo Global chromatin compaction limits the strength of the DNA damage response J. Cell Biol., September 24, 2007; 178(7): 1101 - 1108. [Abstract] [Full Text] [PDF]

				S. E. Golding, E. Rosenberg, S. Neill, P. Dent, L. F. Povirk, and K. Valerie Extracellular Signal-Related Kinase Positively Regulates Ataxia Telangiectasia Mutated, Homologous Recombination Repair, and the DNA Damage Response Cancer Res., February 1, 2007; 67(3): 1046 - 1053. [Abstract] [Full Text] [PDF]

				P. Jeggo and M. Lobrich Radiation-induced DNA damage responses Radiat Prot Dosimetry, December 1, 2006; 122(1-4): 124 - 127. [Abstract] [Full Text] [PDF]

				N. McCabe, N. C. Turner, C. J. Lord, K. Kluzek, A. Bialkowska, S. Swift, S. Giavara, M. J. O'Connor, A. N. Tutt, M. Z. Zdzienicka, et al. Deficiency in the Repair of DNA Damage by Homologous Recombination and Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition Cancer Res., August 15, 2006; 66(16): 8109 - 8115. [Abstract] [Full Text] [PDF]

				K. E. Orii, Y. Lee, N. Kondo, and P. J. McKinnon Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development PNAS, June 27, 2006; 103(26): 10017 - 10022. [Abstract] [Full Text] [PDF]

				X. Wu, S. M. Shell, Z. Yang, and Y. Zou Phosphorylation of Nucleotide Excision Repair Factor Xeroderma Pigmentosum Group A by Ataxia Telangiectasia Mutated and Rad3-Related-Dependent Checkpoint Pathway Promotes Cell Survival in Response to UV Irradiation. Cancer Res., March 15, 2006; 66(6): 2997 - 3005. [Abstract] [Full Text] [PDF]

				B. Hu, H. Wang, X. Wang, H.-R. Lu, C. Huang, S. N. Powell, K. Huebner, and Y. Wang Fhit and CHK1 Have Opposing Effects on Homologous Recombination Repair Cancer Res., October 1, 2005; 65(19): 8613 - 8616. [Abstract] [Full Text] [PDF]