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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Signalling DNA damage by regulating p53 co-factor activity

Linda Smith1, Nicholas B La Thangue

  • 1Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, Scotland, UK.

Cell Cycle (Georgetown, Tex.)
|January 19, 2005
PubMed

Insights

The ATM kinase stabilizes nuclear Strap, enhancing DNA damage response and p53 acetylation. In AT cells, Strap remains cytoplasmic, indicating its crucial role in DNA repair pathways.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • DNA damage triggers signaling pathways involving kinases like ATM and ATR.
  • These kinases phosphorylate targets to facilitate the DNA damage response.
  • The transcriptional co-factor Strap's role in this process was previously unclear.

Purpose of the Study:

  • To elucidate a novel pathway involving ATM and the transcriptional co-factor Strap.
  • To investigate how ATM-mediated phosphorylation affects Strap's cellular localization and function.
  • To determine Strap's contribution to the DNA damage response and p53 acetylation.

Main Methods:

  • Investigated ATM-mediated phosphorylation of Strap.
  • Analyzed the effect of phosphorylation on Strap's nuclear localization and complex formation.
  • Examined Strap's influence on p53 acetylation.
  • Studied Strap localization in cells with and without functional ATM (AT cells).

Main Results:

  • ATM phosphorylates the transcriptional co-factor Strap.
  • Phosphorylation stabilizes nuclear Strap and promotes a stress-responsive co-activator complex.
  • Strap activity enhances p53 acetylation, augmenting the DNA damage response.
  • In AT cells, Strap remains in the cytoplasm, as does an unphosphorylatable mutant.

Conclusions:

  • Strap is a key downstream effector in the DNA damage response pathway.
  • ATM-dependent phosphorylation is critical for Strap's nuclear localization and function.
  • This pathway highlights a novel mechanism for regulating cellular response to DNA damage.

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