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Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation.

Publication ,  Journal Article
Xu, B; Kim, S-T; Lim, D-S; Kastan, MB
Published in: Mol Cell Biol
February 2002

Cell cycle checkpoints are among the multiple mechanisms that eukaryotic cells possess to maintain genomic integrity and minimize tumorigenesis. Ionizing irradiation (IR) induces measurable arrests in the G(1), S, and G(2) phases of the mammalian cell cycle, and the ATM (ataxia telangiectasia mutated) protein plays a role in initiating checkpoint pathways in all three of these cell cycle phases. However, cells lacking ATM function exhibit both a defective G(2) checkpoint and a prolonged G(2) arrest after IR, suggesting the existence of different types of G(2) arrest. Two molecularly distinct G(2)/M checkpoints were identified, and the critical importance of the choice of G(2)/M checkpoint assay was demonstrated. The first of these G(2)/M checkpoints occurs early after IR, is very transient, is ATM dependent and dose independent (between 1 and 10 Gy), and represents the failure of cells which had been in G(2) at the time of irradiation to progress into mitosis. Cell cycle assays that can distinguish mitotic cells from G(2) cells must be used to assess this arrest. In contrast, G(2)/M accumulation, typically assessed by propidium iodide staining, begins to be measurable only several hours after IR, is ATM independent, is dose dependent, and represents the accumulation of cells that had been in earlier phases of the cell cycle at the time of exposure to radiation. G(2)/M accumulation after IR is not affected by the early G(2)/M checkpoint and is enhanced in cells lacking the IR-induced S-phase checkpoint, such as those lacking Nbs1 or Brca1 function, because of a prolonged G(2) arrest of cells that had been in S phase at the time of irradiation. Finally, neither the S-phase checkpoint nor the G(2) checkpoints appear to affect survival following irradiation. Thus, two different G(2) arrest mechanisms are present in mammalian cells, and the type of cell cycle checkpoint assay to be used in experimental investigation must be thoughtfully selected.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

February 2002

Volume

22

Issue

4

Start / End Page

1049 / 1059

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • S Phase
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Nuclear Proteins
  • Mutation
  • Mitosis
  • Humans
  • G2 Phase
  • Flow Cytometry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, B., Kim, S.-T., Lim, D.-S., & Kastan, M. B. (2002). Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol Cell Biol, 22(4), 1049–1059. https://doi.org/10.1128/MCB.22.4.1049-1059.2002
Xu, Bo, Seong-Tae Kim, Dae-Sik Lim, and Michael B. Kastan. “Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation.Mol Cell Biol 22, no. 4 (February 2002): 1049–59. https://doi.org/10.1128/MCB.22.4.1049-1059.2002.
Xu B, Kim S-T, Lim D-S, Kastan MB. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol Cell Biol. 2002 Feb;22(4):1049–59.
Xu, Bo, et al. “Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation.Mol Cell Biol, vol. 22, no. 4, Feb. 2002, pp. 1049–59. Pubmed, doi:10.1128/MCB.22.4.1049-1059.2002.
Xu B, Kim S-T, Lim D-S, Kastan MB. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol Cell Biol. 2002 Feb;22(4):1049–1059.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

February 2002

Volume

22

Issue

4

Start / End Page

1049 / 1059

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • S Phase
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Nuclear Proteins
  • Mutation
  • Mitosis
  • Humans
  • G2 Phase
  • Flow Cytometry