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The ATM-dependent DNA damage signaling pathway.

Publication ,  Journal Article
Kitagawa, R; Kastan, MB
Published in: Cold Spring Harb Symp Quant Biol
2005

Many of the insights that we have gained into the mechanisms involved in cellular DNA damage response pathways have come from studies of human cancer susceptibility syndromes that are altered in DNA damage responses. ATM, the gene mutated in the disorder, ataxia-telangiectasia, is a protein kinase that is a central mediator of responses to DNA double-strand breaks in cells. Recent studies have elucidated the mechanism by which DNA damage activates the ATM kinase and initiates these critical cellular signaling pathways. The SMC1 protein appears to be a particularly important target of the ATM kinase, playing critical roles in controlling DNA replication forks and DNA repair after the damage. A major role for the NBS1 and BRCA1 proteins appears to be in the recruitment of an activated ATM kinase molecule to the sites of DNA breaks so that ATM can phosphorylate SMC1. Generation of mice and cells that are unable to phosphorylate SMC1 demonstrated the importance of SMC1 phosphorylation in the DNA-damage-induced S-phase checkpoint, in determining rates of repair of chromosomal breaks, and in determining cell survival after DNA damage. Focusing on ATM and SMC1, the molecular controls of these pathways is discussed.

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Published In

Cold Spring Harb Symp Quant Biol

DOI

ISSN

0091-7451

Publication Date

2005

Volume

70

Start / End Page

99 / 109

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Substrate Specificity
  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Mutation
  • Models, Biological
  • Mice
  • In Vitro Techniques
  • Humans
 

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Kitagawa, R., & Kastan, M. B. (2005). The ATM-dependent DNA damage signaling pathway. Cold Spring Harb Symp Quant Biol, 70, 99–109. https://doi.org/10.1101/sqb.2005.70.002
Kitagawa, R., and M. B. Kastan. “The ATM-dependent DNA damage signaling pathway.Cold Spring Harb Symp Quant Biol 70 (2005): 99–109. https://doi.org/10.1101/sqb.2005.70.002.
Kitagawa R, Kastan MB. The ATM-dependent DNA damage signaling pathway. Cold Spring Harb Symp Quant Biol. 2005;70:99–109.
Kitagawa, R., and M. B. Kastan. “The ATM-dependent DNA damage signaling pathway.Cold Spring Harb Symp Quant Biol, vol. 70, 2005, pp. 99–109. Pubmed, doi:10.1101/sqb.2005.70.002.
Kitagawa R, Kastan MB. The ATM-dependent DNA damage signaling pathway. Cold Spring Harb Symp Quant Biol. 2005;70:99–109.

Published In

Cold Spring Harb Symp Quant Biol

DOI

ISSN

0091-7451

Publication Date

2005

Volume

70

Start / End Page

99 / 109

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Substrate Specificity
  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Mutation
  • Models, Biological
  • Mice
  • In Vitro Techniques
  • Humans