Structural basis of DNA ligase IV-Artemis interaction in nonhomologous end-joining.
DNA ligase IV (LigIV) and Artemis are central components of the nonhomologous
end-joining (NHEJ) machinery that is required for V(D)J recombination and the
maintenance of genomic integrity in mammalian cells. We report here crystal
structures of the LigIV DNA binding domain (DBD) in both its apo form and in
complex with a peptide derived from the Artemis C-terminal region. We show that
LigIV interacts with Artemis through an extended hydrophobic surface. In
particular, we find that the helix α2 in LigIV-DBD is longer than in other
mammalian ligases and presents residues that specifically interact with the
Artemis peptide, which adopts a partially helical conformation on binding.
Mutations of key residues on the LigIV-DBD hydrophobic surface abolish the
interaction. Together, our results provide structural insights into the
specificity of the LigIV-Artemis interaction and how the enzymatic activities of
the two proteins may be coordinated during NHEJ.