Non-homologous DNA end joining and alternative pathways to double-strand break repair
By Howard H. Y. Chang, Nicholas R. Pannunzio, N. Adachi, M. Lieber. Nature reviews. Molecular cell biology, 2017
1,479 citations recorded by the source corpus.
DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because they can result in the loss of large chromosomal regions. In all mammalian cells, DSBs that occur throughout the cell cycle are repaired predominantly by the non-homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible manner. This flexibility permits NHEJ to function on a wide range of DNA-end configurations, with the resulting repaired DNA junctions often containing mutations. In this Review, we discuss the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations. We also discuss the shunting of DNA-end repair to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA) and the relevance of these different pathways to human disease.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/917bbbde26f47dd351c8dfe0222757e691aecd4d
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In Molecular Biology
Citations in the corpus
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects (2020, background): “Alternatively, NHEJ-mediated repair tends to result in errors because it leads to efficient formation of gene insertion or deletion (indels) in diverse lengths at the DSB site, which eventually causes gene inactivation.(11) If indels occur in the coding sequence, there will be frameshift mutations, ”
- NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “The pathological DSBs are primarily repaired by the NHEJ, a process involves synapsis, end-processing and ligation.(148,149) DNA ligases-mediated DNA end ligation is initialized by adenylating the ligase with an AMP moiety.”