Phosphorylation of Artemis following irradiation-induced DNA damage.
Artemis is a DNA repair factor required for V(D)J recombination, repair of DNA damage induced by ionizing radiation (IR) or radiomimetic drugs, and the maintenance of genome integrity. During V(D)J recombination, Artemis participates in the resolution of hairpin-sealed coding ends, a step crucial to the constitution of the gene encoding for the antigen receptor of lymphocytes. The precise role of Artemis in the repair of IR-induced DNA damage remains to be elucidated. Here we show that Artemis is constitutively phosphorylated in cultured cells and undergoes additional phosphorylation events after irradiation. The IR-induced phosphorylation is mainly, although not solely, dependent on Ataxia-telangiectasia-mutated kinase (ATM). The physiological role of these phosphorylation events remains unknown, as in vitro-generated Artemis mutants, which present impaired IR-induced phosphorylation, still display an activity sufficient to complement the V(D)J recombination defect and the increased radiosensibility of Artemis-deficient cells. Thus, Artemis is an effector of DNA repair that can be phosphorylated by ATM, and possibly by DNA-PKcs and ATR depending upon the type of DNA damage.
Développement Normal et Pathologique du Système Immunitaire (INSERM U429), Hôpital Necker Enfants Malades, Paris, France.
Catherine
C
Poinsignon
Regina
R
de Chasseval
Sebastien
S
Soubeyrand
Despina
D
Moshous
Alain
A
Fischer
Robert J G
RJ
Haché
Jean-Pierre
JP
de Villartay
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000276:immunology; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D011839:Radiation, Ionizing; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C426344:DCLRE1C protein, human; D004720:Endonucleases