Partial deletions of the autoregulatory C-terminal domain of Artemis and their effect on its nuclease activity.

Artemis is a 692 aa nuclease that is essential for opening hairpins during vertebrate V(D)J recombination. Artemis is also important in the DNA repair of double-strand breaks via the nonhomologous DNA end joining (NHEJ) pathway. Therefore, absence of Artemis has been shown to result not only in the blockage of lymphocyte development in vertebrates, but also sensitivity of organisms and cells to double-strand break-inducing events that arise in the course of normal metabolism.

DNA-PKcs chemical inhibition versus genetic mutation: Impact on the junctional repair steps of V(D)J recombination.

Spontaneous DNA-PKcs deficiencies in animals result in a severe combined immunodeficiency (SCID) phenotype because DNA-PKcs is required to activate Artemis for V(D)J recombination coding end hairpin opening. The impact on signal joint formation in these spontaneous mutant mammals is variable. Genetically engineered DNA-PKcs null mice and cells from them show a >1,000-fold reduction in coding joint formation and minimal reduction in signal joint formation during V(D)J recombination.