title: Damaging-agent sensitivity of Artemis-deficient cell lines.
abstract: Defects in repairing double-strand breaks can lead to genome instability and tumorigenesis. In humans, most T(-)B(-) severe combined immunodeficiencies (SCID) have a defect in either the RAG1 or RAG2 gene, are not radiosensitive and do not show genome instability. On the contrary, a minority of T(-)B(-) SCID patients have abnormalities in the Artemis gene and are moderately radiosensitive. Artemis-deficient cells are unable to process hairpin ends after RAG cleavage, but hairpin opening activity alone does not explain the moderate X-ray sensitivity of Artemis-deficient cells. We report here that, at variance with what has been described in mice, cell lines from Artemis(-/-) patients are moderately sensitive to mitomycin C and show only a low to moderate increase in genomic instability, both spontaneously and after exposure to ionizing radiations. There is some heterogeneity in the levels of DNA damage sensitivity and genome instability, which could in part be due to different effects of the specific mutation involved or to genetic background, which may not always represent null alleles. This data supports the hypothesis that, in addition to playing a role in hairpin opening during the V(D)J recombination process, Artemis is involved in the repair of a subset of DNA damage whose exact nature is still undefined.
authors.affiliation: Istituto di Tecnologie Biomediche, CNR, Segrate, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musio
authors.forename: Veronica
authors.initials: V
authors.lastname: Marrella
authors.forename: Cristina
authors.initials: C
authors.lastname: Sobacchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Rucci
authors.forename: Laura
authors.initials: L
authors.lastname: Fariselli
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
authors.forename: Gaetana
authors.initials: G
authors.lastname: Lanzi
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D004720:Endonucleases; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D009153:Mutagens; D009687:Nuclear Proteins; D004720:Endonucleases; C473337:Dclre1c protein, mouse