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Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation.

Publication ,  Journal Article
Xu, B; Kim St, ; Kastan, MB
Published in: Mol Cell Biol
May 2001

Cell cycle arrests in the G(1), S, and G(2) phases occur in mammalian cells after ionizing irradiation and appear to protect cells from permanent genetic damage and transformation. Though Brca1 clearly participates in cellular responses to ionizing radiation (IR), conflicting conclusions have been drawn about whether Brca1 plays a direct role in cell cycle checkpoints. Normal Nbs1 function is required for the IR-induced S-phase checkpoint, but whether Nbs1 has a definitive role in the G(2)/M checkpoint has not been established. Here we show that Atm and Brca1 are required for both the S-phase and G(2) arrests induced by ionizing irradiation while Nbs1 is required only for the S-phase arrest. We also found that mutation of serine 1423 in Brca1, a target for phosphorylation by Atm, abolished the ability of Brca1 to mediate the G(2)/M checkpoint but did not affect its S-phase function. These results clarify the checkpoint roles for each of these three gene products, demonstrate that control of cell cycle arrests must now be included among the important functions of Brca1 in cellular responses to DNA damage, and suggest that Atm phosphorylation of Brca1 is required for the G(2)/M checkpoint.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

May 2001

Volume

21

Issue

10

Start / End Page

3445 / 3450

Location

United States

Related Subject Headings

  • S Phase
  • Nuclear Proteins
  • Humans
  • G2 Phase
  • Developmental Biology
  • Cell Line, Transformed
  • BRCA1 Protein
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

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Xu, B., Kim St, ., & Kastan, M. B. (2001). Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol, 21(10), 3445–3450. https://doi.org/10.1128/MCB.21.10.3445-3450.2001
Xu, B., B. Kim St, and M. B. Kastan. “Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation.Mol Cell Biol 21, no. 10 (May 2001): 3445–50. https://doi.org/10.1128/MCB.21.10.3445-3450.2001.
Xu B, Kim St, Kastan MB. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol. 2001 May;21(10):3445–50.
Xu, B., et al. “Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation.Mol Cell Biol, vol. 21, no. 10, May 2001, pp. 3445–50. Pubmed, doi:10.1128/MCB.21.10.3445-3450.2001.
Xu B, Kim St, Kastan MB. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol. 2001 May;21(10):3445–3450.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

May 2001

Volume

21

Issue

10

Start / End Page

3445 / 3450

Location

United States

Related Subject Headings

  • S Phase
  • Nuclear Proteins
  • Humans
  • G2 Phase
  • Developmental Biology
  • Cell Line, Transformed
  • BRCA1 Protein
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences