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

Xiaoshan Zhang, Janice Succi, Zhaohui Feng, Sheela Prithivirajsingh, Michael D. Story, Randy J. Legerski

Research output: Contribution to journalArticle

95 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9207-9220
Number of pages14
JournalMolecular and Cellular Biology
Volume24
Issue number20
DOIs
StatePublished - Oct 2004

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DNA Damage
Phosphorylation
Ionizing Radiation
V(D)J Recombination
G2 Phase Cell Cycle Checkpoints
Severe Combined Immunodeficiency
Cell Cycle Proteins
Chromosomal Instability
Radiation Tolerance
Cell Cycle Checkpoints
Cell Extracts
Cell Cycle
Phosphotransferases
Maintenance
Mutation
Checkpoint Kinase 1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. / Zhang, Xiaoshan; Succi, Janice; Feng, Zhaohui; Prithivirajsingh, Sheela; Story, Michael D.; Legerski, Randy J.

In: Molecular and Cellular Biology, Vol. 24, No. 20, 10.2004, p. 9207-9220.

Research output: Contribution to journalArticle

Zhang, Xiaoshan ; Succi, Janice ; Feng, Zhaohui ; Prithivirajsingh, Sheela ; Story, Michael D. ; Legerski, Randy J. / Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 20. pp. 9207-9220.
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