ATR Affecting Cell Radiosensitivity Is Dependent on Homologous Recombination Repair but Independent of Nonhomologous End Joining
Open accessAbstract
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.
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In ATM/ATR-deficient cells, the radiosensitive phenotype has been attributed to double-strand break repair defects.
“Moreover, in ATM/ATR-deficient cells, the radiosensitive phenotype has been ascribed to the double-strand break repair defects (26,27).”
The radiosensitive phenotype of ATR kinase-dead cells has been attributed to defects in double-strand break repair.
“The radiosensitive phenotype of ATR kinase-dead cells has been ascribed to the double-strand break repair defects (27).”
From 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 (2006) · cites this paper as [27]
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References 35 · Cited by 130
Research works printed but not linked: 1
- Takata M, Sasaki MS, Sonoda E, et al. Homologous recombination and non-homol- ogous end-joining pathways of DNA double-strand break. EMBO J 1998;17:5497- 508.
- Authors
- Wang, H., Wang, H., Powell, S. N., Iliakis, G., & Wang, Y.
- Affiliations
- Thomas Jefferson University (US)
- Harvard University (US)
- University of Duisburg-Essen (DE)
- Venue
- Cancer Research
- Published
- 2004-10-01
- Volume
- 64
- Issue
- 19
- Pages
- 7139-7143
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2160278162
- Cited by
- 130
- References
- 35
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 11 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration (NAG21628)
- National Institutes of Health (CA56036)
- National Cancer Institute (T-32 CA09137, T32CA009137, P30CA056036, P30 CA 56036)
- Brookhaven National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- ATR kinase, cellular radiosensitivity, homologous recombination repair, non-homologous end joining, DNA double-strand break repair, ionizing radiation, DNA damage checkpoint, doxycycline induction
- MeSH terms
- Cell Line, DNA, DNA Damage, DNA Repair, Doxycycline, Fibroblasts, Humans, Radiation Tolerance, G2 Phase, S Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins
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