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Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway.

Publication ,  Journal Article
Kitagawa, R; Bakkenist, CJ; McKinnon, PJ; Kastan, MB
Published in: Genes Dev
June 15, 2004

The ATM protein kinase is activated by intermolecular autophosphorylation in response to DNA damage and initiates cellular signaling pathways that facilitate cell survival and reduce chromosomal breakage. Here, we show that NBS1 and BRCA1 are required for the recruitment of previously activated ATM to the sites of DNA breaks after ionizing irradiation, and that this recruitment is required for the phosphorylation of SMC1 by ATM. To explore the functional importance of SMC1 phosphorylation, murine cells were generated, in which the two damage-induced phosphorylation sites in SMC1 are mutated. Although these cells demonstrate normal phosphorylation and focus formation of ATM, NBS1, and BRCA1 proteins after IR, they exhibit a defective S-phase checkpoint, decreased survival, and increased chromosomal aberrations after DNA damage. These observations suggest that many of the abnormal stress responses seen in cells lacking ATM, NBS1, or BRCA1 result from a failure of ATM migration to sites of DNA breaks and a resultant lack of SMC1 phosphorylation.

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

June 15, 2004

Volume

18

Issue

12

Start / End Page

1423 / 1438

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Radiation, Ionizing
  • Protein Transport
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Nuclear Proteins
  • Mutation
  • Mice
  • Humans
 

Citation

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Kitagawa, R., Bakkenist, C. J., McKinnon, P. J., & Kastan, M. B. (2004). Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev, 18(12), 1423–1438. https://doi.org/10.1101/gad.1200304
Kitagawa, Risa, Christopher J. Bakkenist, Peter J. McKinnon, and Michael B. Kastan. “Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway.Genes Dev 18, no. 12 (June 15, 2004): 1423–38. https://doi.org/10.1101/gad.1200304.
Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004 Jun 15;18(12):1423–38.
Kitagawa, Risa, et al. “Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway.Genes Dev, vol. 18, no. 12, June 2004, pp. 1423–38. Pubmed, doi:10.1101/gad.1200304.
Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004 Jun 15;18(12):1423–1438.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

June 15, 2004

Volume

18

Issue

12

Start / End Page

1423 / 1438

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Radiation, Ionizing
  • Protein Transport
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Nuclear Proteins
  • Mutation
  • Mice
  • Humans