Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response.
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Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ
Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response.
Mol Cell Biol. 2004 Oct;24(20):9207-20.
- PubMed ID
- 15456891 [ View in PubMed]
- Abstract
Mutations in Artemis in both humans and mice result in severe combined immunodeficiency due to a defect in V(D)J recombination. In addition, Artemis mutants are radiosensitive and chromosomally unstable, which has been attributed to a defect in nonhomologous end joining (NHEJ). We show here, however, that Artemis-depleted cell extracts are not defective in NHEJ and that Artemis-deficient cells have normal repair kinetics of double-strand breaks after exposure to ionizing radiation (IR). Artemis is shown, however, to interact with known cell cycle checkpoint proteins and to be a phosphorylation target of the checkpoint kinase ATM or ATR after exposure of cells to IR or UV irradiation, respectively. Consistent with these findings, our results also show that Artemis is required for the maintenance of a normal DNA damage-induced G2/M cell cycle arrest. Artemis does not appear, however, to act either upstream or downstream of checkpoint kinase Chk1 or Chk2. These results define Artemis as having a checkpoint function and suggest that the radiosensitivity and chromosomal instability of Artemis-deficient cells may be due to defects in cell cycle responses after DNA damage.