biostudies-literatureLee BSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHSCIHR3568-79https://www.ebi.ac.uk/biostudies/studies/S-EPMC3753869biostudies-literatureUnknown33(18)V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcMolecular and cellular biologyFunctional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.PMC3753869GM105404R01 AI047829R01 GM105404691369R01 CA166677AI47829AI074953R01 CA136470P01 CA092584CA92584CA136470R01 AI074953Osipovich ODaniel JALee BSDorsett YZhang SGapud EJHammel MBredemeyer ASleckman BPLees-Miller SCallen ENussenzweig AOltz EMGeorge RBassing CHChen BPfalseFunctional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKc2013-01-01T00:00:00Z2013 Sep2026-05-06T21:38:35.784Z2026-04-07T22:21:53.406ZS-EPMC37538692383688110.1128/mcb.00308-1310.1128/MCB.00308-13