ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining - PubMed (original) (raw)
ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining
Hongyan Wang et al. Cancer Res. 2004.
Abstract
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 G(2) 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 G(2) checkpoints.
Similar articles
- Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants.
Asaad NA, Zeng ZC, Guan J, Thacker J, Iliakis G. Asaad NA, et al. Oncogene. 2000 Nov 23;19(50):5788-800. doi: 10.1038/sj.onc.1203953. Oncogene. 2000. PMID: 11126366 - Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints.
Cliby WA, Roberts CJ, Cimprich KA, Stringer CM, Lamb JR, Schreiber SL, Friend SH. Cliby WA, et al. EMBO J. 1998 Jan 2;17(1):159-69. doi: 10.1093/emboj/17.1.159. EMBO J. 1998. PMID: 9427750 Free PMC article. - DNA double strand break repair inhibition as a cause of heat radiosensitization: re-evaluation considering backup pathways of NHEJ.
Iliakis G, Wu W, Wang M. Iliakis G, et al. Int J Hyperthermia. 2008 Feb;24(1):17-29. doi: 10.1080/02656730701784782. Int J Hyperthermia. 2008. PMID: 18214766 Review. - Role of cell cycle in mediating sensitivity to radiotherapy.
Pawlik TM, Keyomarsi K. Pawlik TM, et al. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):928-42. doi: 10.1016/j.ijrobp.2004.03.005. Int J Radiat Oncol Biol Phys. 2004. PMID: 15234026 Review.
Cited by
- Chemo-Phosphoproteomic Profiling with ATR Inhibitors Berzosertib and Gartisertib Uncovers New Biomarkers and DNA Damage Response Regulators.
Jadav R, Weiland F, Noordermeer SM, Carroll T, Gao Y, Wang J, Zhou H, Lamoliatte F, Toth R, Macartney T, Brown F, Hastie CJ, Alabert C, van Attikum H, Zenke F, Masson JY, Rouse J. Jadav R, et al. Mol Cell Proteomics. 2024 Aug;23(8):100802. doi: 10.1016/j.mcpro.2024.100802. Epub 2024 Jun 15. Mol Cell Proteomics. 2024. PMID: 38880245 Free PMC article. - Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.
Sofianidi A, Dumbrava EE, Syrigos KN, Nasrazadani A. Sofianidi A, et al. Cancers (Basel). 2024 Mar 13;16(6):1139. doi: 10.3390/cancers16061139. Cancers (Basel). 2024. PMID: 38539474 Free PMC article. Review. - Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.
Tam A, Mercier BD, Thomas RM, Tizpa E, Wong IG, Shi J, Garg R, Hampel H, Gray SW, Williams T, Bazan JG, Li YR. Tam A, et al. Cancers (Basel). 2023 Nov 7;15(22):5314. doi: 10.3390/cancers15225314. Cancers (Basel). 2023. PMID: 38001574 Free PMC article. Review. - ATM/Chk2 and ATR/Chk1 Pathways Respond to DNA Damage Induced by Movento® 240SC and Envidor® 240SC Keto-Enol Insecticides in the Germarium of Drosophila melanogaster.
González-Marín B, Calderón-Segura ME, Sekelsky J. González-Marín B, et al. Toxics. 2023 Sep 6;11(9):754. doi: 10.3390/toxics11090754. Toxics. 2023. PMID: 37755764 Free PMC article. - BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1.
Li L, Wang L, Liu D, Zhao Y. Li L, et al. Cell Death Discov. 2023 Aug 25;9(1):313. doi: 10.1038/s41420-023-01611-x. Cell Death Discov. 2023. PMID: 37626049 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous