DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair

Abstract

Activating DNA repair DNA double-strand breaks must be repaired efficiently to avoid cell death or cancer. The break ends can either be directly ligated by nonhomologous end joining (NHEJ) or more accurately repaired by homologous recombination that uses information from the sister chromatid. Sibanda et al. present a high-resolution x-ray structure of a key component of the DNA repair machinery, the DNA-dependent kinase catalytic subunit (DNA-PKcs), bound to a C-terminal peptide of Ku80. The structure suggests that Ku80 presents the DNA ends for repair to a DNA-PKcs dimer and that activity is modulated by interactions between the monomers. Binding of either Ku80 or BRCA1, which may compete for the same binding site on DNA-PKcs, could provide a switch between NHEJ and homologous recombination. Science , this issue p. 520