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

作者：Nicholas R. Pannunzio, Go Watanabe, Michael R. Lieber · 发表于：Journal of Biological Chemistry · 年份：2017 · DOI：10.1074/jbc.tm117.000374 · 被引用次数：504 · 研究领域：DNA Repair Mechanisms、CRISPR and Genetic Engineering、Cancer-related Molecular Pathways

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.