Homologous recombination and non‐homologous end‐joining pathways of DNA double‐strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells
Open accessAbstract
Eukaryotic cells repair DNA double-strand breaks (DSBs) by at least two pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ). Rad54 participates in the first recombinational repair pathway while Ku proteins are involved in NHEJ. To investigate the distinctive as well as redundant roles of these two repair pathways, we analyzed the mutants RAD54(-/-), KU70(-/-) and RAD54(-/-)/KU70(-/-), generated from the chicken B-cell line DT40. We found that the NHEJ pathway plays a dominant role in repairing gamma-radiation-induced DSBs during G1-early S phase while recombinational repair is preferentially used in late S-G2 phase. RAD54(-/-)/KU70(-/-) cells were profoundly more sensitive to gamma-rays than either single mutant, indicating that the two repair pathways are complementary. Spontaneous chromosomal aberrations and cell death were observed in both RAD54(-/-) and RAD54(-/-)/KU70(-/-) cells, with RAD54(-/-)/KU70(-/-) cells exhibiting significantly higher levels of chromosomal aberrations than RAD54(-/-) cells. These observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.
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NHEJ repairs double-strand breaks and infrequently results in insertions or deletions that can disrupt gene function.
“NHEJ operates by recognizing DSBs, processing the DNA ends, and ligating them, infrequently resulting in insertions or deletions (indels) that can disrupt gene function (Stinson & Loparo, 2021; Takata et al., 1998).”
From CRISPR/Cas9 Ribonucleoprotein Nucleofection for Genome Editing in Primary Human Keratinocytes: Knockouts, Deletions, and Homology‐Directed Repair Mutagenesis (2024) · cites this paper as Takata et al., 1998
The Introduction describes NHEJ as joining the ends of a double-strand break and says the resulting junctions can vary in sequence composition. It also identifies Ku and DNA ligase IV as NHEJ components. Our copy does not establish that insertions or deletions occur infrequently, that they disrupt gene function, or the claimed sequence of end-processing steps. (LLM, conf=0.87)
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- Authors
- Takata, M., Sasaki, M. S., Sonoda, E., Morrison, C., Hashimoto, M., Utsumi, H., Yamaguchi‐Iwai, Y., Shinohara, A., & Takeda, S.
- Affiliations
- Kyoto University (JP)
- The University of Osaka (JP)
- Corresponding author
- Takeda, Shunichi
- Venue
- The EMBO Journal
- Published
- 1998-09-15
- Volume
- 17
- Issue
- 18
- Pages
- 5497-5508
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170875
- OpenAlex
- W2058800908
- Cited by
- 1,229
- References
- 1
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 31 · 2023: 29 · 2022: 26 · 2021: 39 · 2020: 32 · 2019: 33 · 2018: 30 · 2017: 36 · 2016: 33 · 2015: 40 · 2014: 36 · 2013: 42 · 2012: 41
- FWCI
- 13.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kindai University
- University of Sussex
- Universität Hamburg
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- University of California, San Francisco
- Bayer Yakuhin
- Japan Society for the Promotion of Science
- Lawrence Livermore 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
- homologous recombination, non-homologous end joining, DNA double-strand break repair, chromosome integrity, Rad54, Ku protein, Ku70, gamma-ray sensitivity, chromosomal abnormalities
- MeSH terms
- Ku Autoantigen, Amino Acid Sequence, Animals, B-Lymphocytes, Cell Line, Chickens, Chromosome Aberrations, Cloning, Molecular, DNA Repair, DNA Helicases, DNA-Binding Proteins, Gamma Rays, Interphase, Molecular Sequence Data, Nuclear Proteins, Radiation Tolerance, Recombination, Genetic, Cell Death, Sequence Homology, Amino Acid, Antigens, Nuclear
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