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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
Summary
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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.

Related Experiment Videos

  • 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.