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J Biol Chem. 2018 Jul 6;293(27):10512-10523. doi: 10.1074/jbc.TM117.000374. Epub 2017 Dec 14.

Nonhomologous DNA end-joining for repair of DNA double-strand breaks.

Author information

1
From the Departments of Pathology, Biochemistry and Molecular Biology, and Molecular Microbiology and Immunology, Section of Molecular and Computational Biology, Department of Biological Sciences, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033.
2
From the Departments of Pathology, Biochemistry and Molecular Biology, and Molecular Microbiology and Immunology, Section of Molecular and Computational Biology, Department of Biological Sciences, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033 lieber@usc.edu.

Abstract

Nonhomologous DNA end-joining (NHEJ) is the predominant double-strand break (DSB) repair pathway throughout the cell cycle and accounts for nearly all DSB repair outside of the S and G2 phases. NHEJ relies on Ku to thread onto DNA termini and thereby improve the affinity of the NHEJ enzymatic components consisting of polymerases (Pol μ and Pol λ), a nuclease (the Artemis·DNA-PKcs complex), and a ligase (XLF·XRCC4·Lig4 complex). Each of the enzymatic components is distinctive for its versatility in acting on diverse incompatible DNA end configurations coupled with a flexibility in loading order, resulting in many possible junctional outcomes from one DSB. DNA ends can either be directly ligated or, if the ends are incompatible, processed until a ligatable configuration is achieved that is often stabilized by up to 4 bp of terminal microhomology. Processing of DNA ends results in nucleotide loss or addition, explaining why DSBs repaired by NHEJ are rarely restored to their original DNA sequence. Thus, NHEJ is a single pathway with multiple enzymes at its disposal to repair DSBs, resulting in a diversity of repair outcomes.

KEYWORDS:

DNA endonuclease; DNA repair; DNA-dependent serine/threonine protein kinase (DNA-PK); NHEJ; double-stranded DNA breaks; nucleic acid enzymology; protein structure

PMID:
29247009
PMCID:
PMC6036208
DOI:
10.1074/jbc.TM117.000374
[Indexed for MEDLINE]
Free PMC Article

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