Damaging-agent sensitivity of Artemis-deficient cell lines

Antonio Musio, Veronica Marrella, Cristina Sobacchi, Francesca Rucci, Laura Fariselli, Silvia Giliani, Gaetana Lanzi, Luigi D. Notarangelo, Domenico Delia, Roberto Colombo, Paolo Vezzoni, Anna Villa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1250-1256
Number of pages7
JournalEuropean Journal of Immunology
Volume35
Issue number4
DOIs
Publication statusPublished - Apr 2005

Fingerprint

Genomic Instability
Cell Line
Severe Combined Immunodeficiency
DNA Damage
V(D)J Recombination
Mitomycin
Ionizing Radiation
Genes
Carcinogenesis
Alleles
X-Rays
Mutation

Keywords

  • Artemis
  • Cisplatin
  • Interstrand cross-link
  • Mitomycin C
  • Molecular biology

ASJC Scopus subject areas

  • Immunology

Cite this

Damaging-agent sensitivity of Artemis-deficient cell lines. / Musio, Antonio; Marrella, Veronica; Sobacchi, Cristina; Rucci, Francesca; Fariselli, Laura; Giliani, Silvia; Lanzi, Gaetana; Notarangelo, Luigi D.; Delia, Domenico; Colombo, Roberto; Vezzoni, Paolo; Villa, Anna.

In: European Journal of Immunology, Vol. 35, No. 4, 04.2005, p. 1250-1256.

Research output: Contribution to journalArticle

Musio, Antonio ; Marrella, Veronica ; Sobacchi, Cristina ; Rucci, Francesca ; Fariselli, Laura ; Giliani, Silvia ; Lanzi, Gaetana ; Notarangelo, Luigi D. ; Delia, Domenico ; Colombo, Roberto ; Vezzoni, Paolo ; Villa, Anna. / Damaging-agent sensitivity of Artemis-deficient cell lines. In: European Journal of Immunology. 2005 ; Vol. 35, No. 4. pp. 1250-1256.
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