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.
Highlights
Nonhomologous DNA end-joining (NHEJ) is the predominant double-strand break (DSB) repair pathway throughout the cell cycle and accounts for most double-strand breaks (DSBs) 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 and Pol ), a nuclease, and a ligase (XLF1⁄7XRCC41⁄7Lig4 complex)
Nonhomologous DNA end-joining (NHEJ) was originally a phrase used to describe a type of illegitimate repair that utilizes little to no long homology [2]
Summary
Nonhomologous DNA end-joining (NHEJ) is the predominant double-strand break (DSB) repair pathway throughout the cell cycle and accounts for most DSB repair outside of the S and G2 phases. Bank; NHEJ, nonhomologous DNA end joining; Pol, polymerase; HR, homologous recombination; aa, amino acid; SSA, single-strand annealing; TdT, terminal deoxynucleotidyltransferase; 3Ј-PG, Ј-phosphoglycolate; PNK, polynucleotide kinase; CtIP, C-terminal-binding protein interacting protein; XLF, XRCC4-like factor; ssDNA, single-stranded DNA; dsDNA, double-stranded DNA; a-EJ, alternative end-joining; nt, nucleotide Repair mechanisms can be largely divided between those that use extensive homology from a sister chromatid or homologous sequence elsewhere in the genome and those that use little to no homology Both mechanisms require end processing by nucleases, utilization of DNA polymerases, and a final ligation step to complete repair of the broken DNA (Fig. 1). We provide a brief overview of the types of proteins that are involved in NHEJ and their functions, which applies to most vertebrates
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