The Mechanism of Human Nonhomologous DNA End Joining*

By M. Lieber. Journal of Biological Chemistry, 2008

739 citations recorded by the source corpus.

Double-strand breaks are common in all living cells, and there are two major pathways for their repair. In eukaryotes, homologous recombination is restricted to late S or G2, whereas nonhomologous DNA end joining (NHEJ) can occur throughout the cell cycle and is the major pathway for the repair of double-strand breaks in multicellular eukaryotes. NHEJ is distinctive for the flexibility of the nuclease, polymerase, and ligase activities that are used. This flexibility permits NHEJ to function on the wide range of possible substrate configurations that can arise when double-strand breaks occur, particularly at sites of oxidative damage or ionizing radiation. NHEJ does not return the local DNA to its original sequence, thus accounting for the wide range of end results. Part of this heterogeneity arises from the diversity of the DNA ends, but much of it arises from the many alternative ways in which the nuclease, polymerases, and ligase can act during NHEJ. Physiologic double-strand break processes make use of the imprecision of NHEJ in generating antigen receptor diversity. Pathologically, the imprecision of NHEJ contributes to genome mutations that arise over time.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9e2fd1727ad781ba448906cf61429e97cf4bb660

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In Molecular Biology

1. M. Lieber
2. Stephen P. Jackson
3. J. Bartek
4. Feng Zhang
5. W. Gu
6. A. Sica
7. P. Allavena
8. J. R. Lupski

Citations in the corpus

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• Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis (2010, neutral): “DSBs can also be repaired by NHEJ, a distinct but efficient pathway in which non-homologous DNA ends are joine”
• Repair of ionizing radiation-induced DNA double strand breaks by non-homologous end-joining (2009, background): “and Lieber, M. R. (2005) The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human Artemis. J. Biol. Chem. 280, 33839–33846 66 Chen, B. P., Chan, D. W., Kobayashi, J., Burma, S., Asaithamby, A., Morotomi-Yano, K., Botvinick, E., Qin, J. and Chen, D. J. (2005) Cell cycle depen”
• Comparison of nonhomologous end joining and homologous recombination in human cells (2008, background): “NHEJ modifies the broken DNA ends, and ligates them together with no regard for homology, generating deletions or insertions [2].”
• Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. (2009, background): “There are two major mechanisms for DSB repair, homologous recombination (HR) [165] and non-homologous end-joining (NHEJ) [166].”
• The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End Joining Pathway (2010, background): “Ku bound to a DNA end can be considered as a Ku:DNA complex, which serves as a node at which the nuclease, polymerases, and ligase of NHEJ can dock (31).”
• Mechanisms for human genomic rearrangements (2008, background): “This process determines the two important characteristics of NHEJ: first, neither LCRs nor MEPS are obligatorily required for NHEJ; and second, NHEJ leaves an 'information scar' [71] at the”