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UV-induced damage to DNA: effect of cytosine methylation on pyrimidine dimerization

Lara Martinez-Fernandez1, Akos Banyasz2, Luciana Esposito1

  • 1Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy.

Signal Transduction and Targeted Therapy
|December 22, 2017
PubMed

Insights

Cytosine methylation, crucial for epigenetics and cancer, enhances UV-induced DNA damage. Methylated cytosine alters DNA structure and electronic properties, increasing susceptibility to mutations like pyrimidine dimers.

Area of Science:

  • Epigenetics and Molecular Biology
  • Photochemistry and DNA Damage

Background:

  • Cytosine methylation is a key epigenetic mechanism involved in gene regulation and cellular signaling.
  • Reversible epigenetic modifications, like methylation/demethylation, present therapeutic targets, particularly in cancer.
  • Methylated DNA sites are frequently observed at mutational hotspots in skin cancers.

Discussion:

  • This review examines the physicochemical factors influencing ultraviolet (UV)-induced DNA damage in methylated cytosine.
  • Focuses on the formation of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone adducts.
  • Investigates how cytosine methylation alters spectral properties, excited state lifetimes, and DNA duplex rigidity.

Key Insights:

  • Methylation causes a red-shift in absorption spectra and extends excited state lifetimes of cytosine.
  • Altered sugar puckering and increased DNA duplex rigidity due to methylation favor pyrimidine dimerization.
  • These changes enhance the susceptibility of methylated cytosine to UV-induced mutagenic lesions.

Outlook:

  • Understanding these UV-induced reactivity changes in methylated cytosine is vital for developing targeted cancer therapies.
  • Further research can elucidate the precise role of these factors in skin carcinogenesis.
  • Exploring the interplay between epigenetic modifications and DNA damage response pathways is crucial.

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