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Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response.

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.

Pubmed ID: 15456891

Authors

  • Zhang X
  • Succi J
  • Feng Z
  • Prithivirajsingh S
  • Story MD
  • Legerski RJ

Journal

Molecular and cellular biology

Publication Data

October 30, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA52461
  • Agency: NCI NIH HHS, Id: CA90270
  • Agency: NCI NIH HHS, Id: CA96574
  • Agency: NIEHS NIH HHS, Id: ES07784

Mesh Terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Division
  • Checkpoint Kinase 2
  • Chromosomal Instability
  • DNA
  • DNA Damage
  • DNA Repair
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins
  • G2 Phase
  • Humans
  • Mice
  • Nuclear Proteins
  • Phosphorylation
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Radiation, Ionizing
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • Ultraviolet Rays