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

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

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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Crossref · 10.1146/annurev.biochem.052308.093131

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  • Some non-recurrent deletion CNVs have 2-20 bp of microhomology at their breakpoints and are predicted to arise through MMEJ.

    “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

  • NHEJ repairs breaks induced by ionizing radiation, oxidative free radicals, misappropriate enzymatic action at sensitive sites, inhibition of topoisomerases, and other mechanical stresses.

    “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].”

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  1. [25]Wilson TE Nonhomologous recombination. Encyclopedia of Chemical Biology 2008 Wiley

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Authors
Lieber, M. R.
Affiliations
University of Southern California (US)
Corresponding author
Lieber, Michael R.
Venue
Annual Review of Biochemistry
Published
2010-06-07
Volume
79
Issue
1
Pages
181-211
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
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
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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