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

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 compon...

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Bibliographic Details
Published inThe Journal of biological chemistry Vol. 293; no. 27; pp. 10512 - 10523
Main Authors Pannunzio, Nicholas R., Watanabe, Go, Lieber, Michael R.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 06.07.2018
American Society for Biochemistry and Molecular Biology
Subjects
Animals
DNA Breaks, Double-Stranded
DNA End-Joining Repair
DNA endonuclease
DNA repair
DNA-dependent serine/threonine protein kinase (DNA-PK)
double-stranded DNA breaks
Humans
Ku Autoantigen - metabolism
NHEJ
nucleic acid enzymology
protein structure
Thematic Minireviews
protein structure
DNA-dependent serine/threonine protein kinase (DNA-PK)
DNA endonuclease
nucleic acid enzymology
double-stranded DNA breaks
NHEJ
DNA repair
Online AccessGet full text
ISSN0021-9258
1083-351X
1083-351X
DOI10.1074/jbc.TM117.000374

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Summary: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.
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Edited by Patrick Sung
Both authors contributed equally to this work.
ISSN:0021-9258
1083-351X
1083-351X
DOI:10.1074/jbc.TM117.000374