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Inhibition of transcription factor binding by ultraviolet-induced pyrimidine dimers

S Tommasi1, P M Swiderski, Y Tu

  • 1Department of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.

Biochemistry
|December 10, 1996
PubMed

Insights

Ultraviolet (UV) light causes DNA damage, forming pyrimidine dimers that block essential transcription factors. This interference with DNA binding may significantly contribute to UV radiation

Area of Science:

  • Molecular Biology
  • Photochemistry
  • Genetics

Background:

  • Ultraviolet (UV) light exposure induces DNA damage, primarily through the formation of cis-syn cyclobutane pyrimidine dimers (pyrimidine dimers).
  • These DNA lesions are mutagenic and can disrupt crucial DNA-dependent cellular processes.
  • The impact of pyrimidine dimers on the recognition of DNA sequences by trans-acting factors remains an area of investigation.

Purpose of the Study:

  • To investigate the effect of site-specific pyrimidine dimers on the binding affinity of key transcription factors to their DNA recognition sequences.
  • To determine if UV-induced DNA lesions interfere with the function of transcription factors involved in cell cycle regulation and DNA damage response.

Main Methods:

  • Incorporation of site-specific T-T dimers into synthetic oligonucleotides containing recognition sites for transcription factors E2F, NF-Y, AP-1, NF-kappa B, and p53.
  • Assessment of transcription factor binding to damaged versus undamaged DNA sequences using electrophoretic mobility shift assays or similar techniques.

Main Results:

  • The presence of pyrimidine dimers in DNA recognition sequences significantly inhibited the binding of all tested transcription factors.
  • The reduction in transcription factor binding affinity ranged from 11-fold to 60-fold.
  • This indicates that the most frequent UV-induced DNA lesion severely impairs the interaction of DNA with critical regulatory proteins.

Conclusions:

  • The common UV-induced DNA lesion, pyrimidine dimers, can profoundly interfere with the binding of essential transcription factors involved in cell cycle control and DNA damage response.
  • Inhibition of transcription factor binding by pyrimidine dimers is proposed as a major biological consequence of UV radiation.
  • Inefficient repair of promoter regions and the broad impact of UV damage on various transcription factors support this hypothesis.

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