Poinsignon Catherine, de Chasseval Regina, Soubeyrand Sebastien, Moshous Despina, Fischer Alain, Haché Robert J G, de Villartay Jean-Pierre
Développement Normal et Pathologique du Système Immunitaire (INSERM U429), Hôpital Necker Enfants Malades, Paris, France.
Eur J Immunol. 2004 Nov;34(11):3146-55. doi: 10.1002/eji.200425455.
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.
Artemis是V(D)J重组、电离辐射（IR）或放射模拟药物诱导的DNA损伤修复以及基因组完整性维持所必需的一种DNA修复因子。在V(D)J重组过程中，Artemis参与发夹封闭的编码末端的解旋，这是淋巴细胞抗原受体编码基因构成的关键步骤。Artemis在IR诱导的DNA损伤修复中的精确作用仍有待阐明。在此我们表明，Artemis在培养细胞中组成性磷酸化，并在照射后经历额外的磷酸化事件。IR诱导的磷酸化主要（尽管不是唯一）依赖于共济失调毛细血管扩张症突变激酶（ATM）。这些磷酸化事件的生理作用仍然未知，因为体外产生的Artemis突变体，其IR诱导的磷酸化受损，但仍显示出足以弥补V(D)J重组缺陷和Artemis缺陷细胞放射敏感性增加的活性。因此，Artemis是一种DNA修复效应因子，可被ATM磷酸化，并且可能根据DNA损伤的类型被DNA-PKcs和ATR磷酸化。
