期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 27, 页码 10512-10523出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.TM117.000374
关键词
DNA repair; nucleic acid enzymology; protein structure; DNA endonuclease; DNA-dependent serine; threonine protein kinase (DNA-PK); double-stranded DNA breaks; NHEJ
资金
- National Institutes of Health
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 G(2) phases. NHEJ relies on Ku to thread onto DNA termini and thereby improve the affinity of the NHEJ enzymatic components consisting of polymerases (Pol and Pol ), a nuclease (the ArtemisDNA-PKcs complex), and a ligase (XLFXRCC4Lig4 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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