The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End Joining Pathway
By M. Lieber. Annual Review of Biochemistry, 2010
2,827 citations recorded by the source corpus.
Double-strand DNA breaks are common events in eukaryotic cells, and there are two major pathways for repairing them: homologous recombination and nonhomologous DNA end joining (NHEJ). The diverse causes of 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, 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 V(D)J recombination and class switch recombination. Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation, but also severely immunodeficient.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/18fbc555b8b4f5dc904582d8d0f5db46cdc30052
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Citations in the corpus
- RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection (2013, background): “As NHEJ operates independently of DNA sequence, it is intrinsically error prone and can drive chromosome translocations by joining DSBs from different parts of the genome (Elliott and Jasin, 2002; Lieber, 2010).”
- Genome editing with engineered zinc finger nucleases (2010, background): “All eukaryotic cells efficiently repair DSBs via the homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathway”
- Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. (2013, background): “Homologous recombination provides greater repair fidelity than NHEJ, the latter being the major pathway to repair prompt DSB throughout all phases of the cell cycle (reviewed in [33,34]).”
- HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B (2015, background): “As NHEJ is error-prone, 47 48 many of these molecules are functionally defective.”