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Ionizing radiation activates the ATM kinase throughout the cell cycle.

Publication ,  Journal Article
Pandita, TK; Lieberman, HB; Lim, DS; Dhar, S; Zheng, W; Taya, Y; Kastan, MB
Published in: Oncogene
March 9, 2000

The ATM protein kinase is a critical intermediate in a number of cellular responses to ionizing irradiation (IR) and possibly other stresses. ATM dysfunction results in abnormal checkpoint responses in multiple phases of the cell cycle, including G1, S and G2. Though downstream targets of the ATM kinase are still being elucidated, it has been demonstrated that ATM acts upstream of p53 in a signal transduction pathway initiated by IR and can phosphorylate p53 at serine 15. The cell cycle stage-specificity of ATM activation and p53Ser15 phosphorylation was investigated in normal lymphoblastoid cell line (GM536). Ionizing radiation was found to enhance the kinase activity of ATM in all phases of the cell cycle. This enhanced activity was apparent immediately after treatment of cells with IR, but was not accompanied by a change in the abundance of the ATM protein. Since IR activates the ATM kinase in all phases of the cell cycle, DNA replication-dependent strand breaks are not required for this activation. Further, since p53 protein is not directly required for IR-induced S and G2-phase checkpoints, the ATM kinase likely has different functional targets in different phases of the cell cycle. These observations indicate that the ATM kinase is necessary primarily for the immediate response to DNA damage incurred in all phases of the cell cycle.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

March 9, 2000

Volume

19

Issue

11

Start / End Page

1386 / 1391

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Serine
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Gamma Rays
  • G2 Phase
 

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Pandita, T. K., Lieberman, H. B., Lim, D. S., Dhar, S., Zheng, W., Taya, Y., & Kastan, M. B. (2000). Ionizing radiation activates the ATM kinase throughout the cell cycle. Oncogene, 19(11), 1386–1391. https://doi.org/10.1038/sj.onc.1203444
Pandita, T. K., H. B. Lieberman, D. S. Lim, S. Dhar, W. Zheng, Y. Taya, and M. B. Kastan. “Ionizing radiation activates the ATM kinase throughout the cell cycle.Oncogene 19, no. 11 (March 9, 2000): 1386–91. https://doi.org/10.1038/sj.onc.1203444.
Pandita TK, Lieberman HB, Lim DS, Dhar S, Zheng W, Taya Y, et al. Ionizing radiation activates the ATM kinase throughout the cell cycle. Oncogene. 2000 Mar 9;19(11):1386–91.
Pandita, T. K., et al. “Ionizing radiation activates the ATM kinase throughout the cell cycle.Oncogene, vol. 19, no. 11, Mar. 2000, pp. 1386–91. Pubmed, doi:10.1038/sj.onc.1203444.
Pandita TK, Lieberman HB, Lim DS, Dhar S, Zheng W, Taya Y, Kastan MB. Ionizing radiation activates the ATM kinase throughout the cell cycle. Oncogene. 2000 Mar 9;19(11):1386–1391.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

March 9, 2000

Volume

19

Issue

11

Start / End Page

1386 / 1391

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Serine
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Gamma Rays
  • G2 Phase