DNA and Chromosomes
Effects of DNA end configuration on XRCC4-DNA ligase IV and its stimulation of Artemis activity
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4-DNA ligase IV (X4-LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5′ and 3′ overhangs.Unifying the DNA End-processing Roles of the Artemis Nuclease: KU-DEPENDENT ARTEMIS RESECTION AT BLUNT DNA ENDS
Background: Artemis is a nuclease that is necessary for hairpin opening in V(D)J recombination.Results: Artemis action on blunt DNA ends is dependent on DNA sequence (breathing) and Ku.Conclusion: Breathing of blunt DNA ends into a transient ss/dsDNA boundary is needed for Artemis action.Significance: Unification of Artemis nuclease action explains the features of NHEJ and V(D)J recombination.
