Nonhomologous end joining and V (D) J recombination require an additional factor
Y Dai, B Kysela, LA Hanakahi… - Proceedings of the …, 2003 - National Acad Sciences
Y Dai, B Kysela, LA Hanakahi, K Manolis, E Riballo, M Stumm, TO Harville, SC West…
Proceedings of the National Academy of Sciences, 2003•National Acad SciencesDNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-
strand breaks in mammalian cells. It also functions to carry out rearrangements at the
specialized breaks introduced during V (D) J recombination. Here, we describe a patient
with T− B− severe combined immunodeficiency, whose cells have defects closely
resembling those of NHEJ-defective rodent cells. Cells derived from this patient show
dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in …
strand breaks in mammalian cells. It also functions to carry out rearrangements at the
specialized breaks introduced during V (D) J recombination. Here, we describe a patient
with T− B− severe combined immunodeficiency, whose cells have defects closely
resembling those of NHEJ-defective rodent cells. Cells derived from this patient show
dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in …
DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T−B− severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue in Saccharomyces cerevisiae functions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals.
National Acad Sciences