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The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway
Open accessAbstract
Double-strand DNA breaks are common events in eukaryotic cells, and there are two major pathways for repairing them: homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). The various causes of double-strand breaks (DSBs) result in a diverse chemistry of DNA ends that must be repaired. Across NHEJ evolution, the enzymes of the NHEJ pathway exhibit a remarkable degree of structural tolerance in the range of DNA end substrate configurations upon which they can act. In vertebrate cells, the nuclease, DNA polymerases, and ligase of NHEJ are the most mechanistically flexible and multifunctional enzymes in each of their classes. Unlike repair pathways for more defined lesions, NHEJ repair enzymes act iteratively, act in any order, and can function independently of one another at each of the two DNA ends being joined. NHEJ is critical not only for the repair of pathologic DSBs as in chromosomal translocations, but also for the repair of physiologic DSBs created during variable (diversity) joining [V(D)J] recombination and class switch recombination (CSR). Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient.
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“Breakpoints of some non-recurrent deletion CNVs have sequences with very short (2–20 basepairs) stretches of nucleotide identity. These are predicted to be formed by an alternative microhomology mediated end joining (MMEJ) mechanism (Lieber, 2010).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Lieber, 2010
In the citing paper
“DNA double-strand break repair or non-homologous end joining (NHEJ) repairs breaks induced by ionizing radiation (IR), oxidative free radicals, misappropriate enzymatic action at sensitive sites, inhibition of topoisomerases, and other mechanical stresses [54].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [54]
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Metadata
- Authors
- Lieber, M. R.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Lieber, Michael R.
- ORCID
- Lieber, Michael R.
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2010-06-07
- Volume
- 79
- Issue
- 1
- Pages
- 181-211
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC3079308
- OpenAlex
- W2164995160
- Cited by
- 2,882
- References
- 168
- Citations by year
- 2026: 103 · 2025: 144 · 2024: 176 · 2023: 148 · 2022: 199 · 2021: 238 · 2020: 209 · 2019: 187 · 2018: 201 · 2017: 215 · 2016: 212 · 2015: 183 · 2014: 199 · 2013: 168 · 2012: 148
- FWCI
- 13.03
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA100504)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- DNA double-strand break repair, non-homologous end joining, homologous recombination, DNA ligase IV, DNA polymerase IV, chromosomal translocation, V(D)J recombination, class switch recombination, immunodeficiency, radiosensitivity
- MeSH terms
- Animals, Deoxyribonucleases, DNA-Directed DNA Polymerase, DNA Repair, Humans, DNA Ligases, DNA Breaks, Double-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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