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...

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Bibliographic Details
Published in:European journal of immunology 2004-11, Vol.34 (11), p.3146-3155
Main Authors: Poinsignon, Catherine, de Chasseval, Regina, Soubeyrand, Sebastien, Moshous, Despina, Fischer, Alain, Haché, Robert J. G., de Villartay, Jean‐Pierre
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Animals
Artemis
Ataxia Telangiectasia Mutated Proteins
ATM
Blotting, Western
Cell Cycle Proteins - immunology
CHO Cells
Cricetinae
DNA - radiation effects
DNA damage
DNA Damage - physiology
DNA Repair - physiology
DNA-Binding Proteins
DNA‐PKcs
Endonucleases
Fibroblasts - immunology
Humans
IR‐induced phosphorylation
Kinetics
Molecular Sequence Data
Nuclear Proteins - genetics
Nuclear Proteins - immunology
Nuclear Proteins - metabolism
Phosphorylation
Point Mutation
Protein-Serine-Threonine Kinases - immunology
Radiation, Ionizing
Sequence Alignment
Tumor Suppressor Proteins
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Summary: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.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200425455