Physical ARTEMIS:DNA-PKcs interaction is necessary for V(D)J recombination.

ABSTRACT: The nuclease ARTEMIS and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are involved in the repair of physiological and pathogenic DNA double strand breaks. Both proteins are indispensable for the hairpin-opening activity in V(D)J recombination and therefore essential for the adaptive immune response. ARTEMIS and DNA-PKcs interact, however experimental evidence for in vivo significance is missing. We demonstrate that mutations abolishing this protein-protein interaction affect nuclease function. In DNA-PKcs, mutation L3062R impairs the physical interaction with ARTEMIS and was previously identified as pathogenic variant, resulting in radiosensitive severe combined immunodeficiency. In ARTEMIS, specific mutations in two conserved regions affect interaction with DNA-PKcs. In c

SUBMITTER: Niewolik D 

PROVIDER: S-EPMC8887466 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature