Cited by 2,882DNA Repair MechanismsEffects of Radiation ExposureCRISPR and Genetic Engineering

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The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway

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Lieber, Michael R.·2010·Annual Review of Biochemistry

DOI 10.1146/annurev.biochem.052308.093131PMC PMC3079308

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Abstract

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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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
DOI: 10.1146/annurev.biochem.052308.093131
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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The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway

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