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Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation.

Publication ,  Journal Article
Xu, B; O'Donnell, AH; Kim, S-T; Kastan, MB
Published in: Cancer Res
August 15, 2002

Although it is well established that inheritance of mutations in the Brca1 gene significantly increases the chances of developing breast or ovarian cancers, the mechanisms underlying this specific tumor susceptibility remain to be clarified. It is clear that one of the roles of the Brca1 protein is to facilitate cellular responses to DNA damage. We recently reported that Brca1 function is required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. We also found that mutation of serine 1423 in Brca1, a target of Atm phosphorylation, abrogates the G2-M checkpoint but not the ionizing irradiation-induced S-phase checkpoint. Here we demonstrate that mutation of serine 1387 in Brca1, another target of Atm phosphorylation, conversely abrogates the radiation-induced S-phase arrest but does not affect the G2-M checkpoint. Thus, these two posttranslational modifications of Brca1 have two distinct functional roles in the protein. In addition, although mutation of this site abrogates the ionizing irradiation-induced S-phase arrest, it does not adversely affect cell survival after irradiation. This demonstrates that loss of this checkpoint function by itself does not affect cell survival and suggests that some other function of Brca1 alters cell survival after DNA damage.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 15, 2002

Volume

62

Issue

16

Start / End Page

4588 / 4591

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Serine
  • S Phase
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Mutation
 

Citation

APA
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ICMJE
MLA
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Xu, B., O’Donnell, A. H., Kim, S.-T., & Kastan, M. B. (2002). Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res, 62(16), 4588–4591.
Xu, Bo, Anne H. O’Donnell, Seong-Tae Kim, and Michael B. Kastan. “Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation.Cancer Res 62, no. 16 (August 15, 2002): 4588–91.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 15, 2002

Volume

62

Issue

16

Start / End Page

4588 / 4591

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Serine
  • S Phase
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Mutation