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Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis

S Hasan1, P O Hassa, R Imhof

  • 1institute of Veterinary Biochemistry, University of Zürich, Switzerland.

Nature
|March 27, 2001
PubMed

Insights

The transcriptional coactivator p300 interacts with proliferating cell nuclear antigen (PCNA), suggesting a role in DNA repair synthesis. This interaction aids in chromatin remodeling at DNA damage sites, facilitating DNA repair.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The transcriptional coactivator p300 is crucial for various biological processes, including cell differentiation and growth control.
  • Mouse embryos lacking p300 exhibit developmental defects and reduced DNA synthesis, indicating a potential role in cell proliferation and DNA integrity.

Purpose of the Study:

  • To investigate the potential role of p300 in DNA repair synthesis.
  • To explore the interaction between p300 and proliferating cell nuclear antigen (PCNA).

Main Methods:

  • In vitro and in vivo complex formation assays between p300 and PCNA.
  • Cellular localization studies using microscopy to observe p300 and PCNA colocalization.
  • In vitro DNA synthesis assays using the p300-PCNA complex.
  • Chromatin immunoprecipitation (ChIP) experiments after ultraviolet (UV) irradiation.

Main Results:

  • p300 forms a stable complex with PCNA, independent of the cell cycle phase.
  • Both p300 and PCNA exhibit significant colocalization in nuclear speckles.
  • The endogenous p300-PCNA complex was shown to stimulate DNA synthesis in vitro.
  • Chromatin immunoprecipitation revealed p300 association with newly synthesized DNA following UV-induced DNA damage.

Conclusions:

  • p300 interacts with PCNA and plays a role in DNA repair synthesis.
  • p300 likely participates in chromatin remodeling at DNA lesion sites.
  • This remodeling facilitates PCNA's function in DNA repair, highlighting a novel mechanism for maintaining genomic stability.

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