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ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.

Publication ,  Journal Article
Lim, DS; Kim, ST; Xu, B; Maser, RS; Lin, J; Petrini, JH; Kastan, MB
Published in: Nature
April 6, 2000

The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

April 6, 2000

Volume

404

Issue

6778

Start / End Page

613 / 617

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transfection
  • Signal Transduction
  • Serine
  • S Phase
  • Recombinant Fusion Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases
 

Citation

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Lim, D. S., Kim, S. T., Xu, B., Maser, R. S., Lin, J., Petrini, J. H., & Kastan, M. B. (2000). ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature, 404(6778), 613–617. https://doi.org/10.1038/35007091
Lim, D. S., S. T. Kim, B. Xu, R. S. Maser, J. Lin, J. H. Petrini, and M. B. Kastan. “ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.Nature 404, no. 6778 (April 6, 2000): 613–17. https://doi.org/10.1038/35007091.
Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH, et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature. 2000 Apr 6;404(6778):613–7.
Lim, D. S., et al. “ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.Nature, vol. 404, no. 6778, Apr. 2000, pp. 613–17. Pubmed, doi:10.1038/35007091.
Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH, Kastan MB. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature. 2000 Apr 6;404(6778):613–617.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

April 6, 2000

Volume

404

Issue

6778

Start / End Page

613 / 617

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transfection
  • Signal Transduction
  • Serine
  • S Phase
  • Recombinant Fusion Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases