Transcription factors, nucleotide excision repair, and cancer: A review of molecular interplay

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• Bulky DNA adducts, often from external sources like UV radiation and smoking, can lead to cancer-driving mutations if not repaired by nucleotide excision repair (NER).
• Transcription factors (TFs) play a crucial role in modulating DNA adduct formation and NER efficiency at their binding sites.
• TF binding sites can become mutation hotspots, as seen with UV-induced cyclobutane pyrimidine dimers (CPDs) in melanoma, linked to inhibited repair.

Purpose of the Study:

• To review the complex interplay between transcription factors (TFs) and nucleotide excision repair (NER) in the context of cancer development and progression.
• To highlight how TFs influence DNA adduct formation, repair dynamics, and subsequent mutation accumulation.
• To explore the dual role of TFs in regulating oncogenic and anti-oncogenic pathways, independent of NER.

Main Methods:

• Literature review focusing on the molecular mechanisms of DNA adduct formation and repair.
• Analysis of studies investigating the role of transcription factors in DNA damage response pathways.
• Examination of research on TF binding site characteristics and their association with mutation hotspots in cancer.

Main Results:

• Transcription factors can significantly impact the formation and repair of DNA adducts at their binding sites.
• TF overexpression in response to DNA damaging agents can activate signaling pathways relevant to cancer.
• Specific TF binding sites are associated with increased susceptibility to mutations, contributing to cancer initiation and progression.

Conclusions:

• The interaction between transcription factors and nucleotide excision repair is a critical determinant in cancer development.
• Understanding these interactions offers potential targets for cancer prevention and therapy.
• TFs represent key regulators in the DNA damage response, influencing both mutation susceptibility and cellular signaling in cancer.