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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
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“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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“If necessary, this process may involve a small degree of end-processing (either gap-filling or ssDNA-trimming) to create compatible DNA ends (Lieber, 2010).”
BackgroundDifferential DNA repair pathway choice in cancer cells after proton- and photon-irradiation
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Self-citationPrecise and efficient scarless genome editing in stem cells using CORRECT
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The capacity of oocytes for DNA repair
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Mycobacteria exploit three genetically distinct DNA double‐strand break repair pathways
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CRISPR/Cas9-mediated genome engineering of CHO cell factories: application and perspectives
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PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice
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XLF regulates filament architecture of the XRCC4.ligase IV complex
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DNA Repair Pathways and Mechanisms
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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
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