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

Abstract

Bulky DNA adducts are mostly formed by external factors such as UV irradiation, smoking or treatment with DNA crosslinking agents. If such DNA adducts are not removed by nucleotide excision repair, they can lead to formation of driver mutations that contribute to cancer formation. Transcription factors (TFs) may critically affect both DNA adduct formation and repair efficiency at the binding site to DNA. For example, "hotspot" mutations in melanoma coincide with UV-induced accumulated cyclobutane pyrimidine dimer (CPD) adducts and/or inhibited repair at the binding sites of some TFs. Similarly, anticancer treatment with DNA cross-linkers may additionally generate DNA adducts leading to secondary mutations and the formation of malignant subclones. In addition, some TFs are overexpressed in response to UV irradiation or chemotherapeutic treatment, activating oncogenic and anti-oncogenic pathways independently of nucleotide excision repair itself. This review focuses on the interplay between TFs and nucleotide excision repair during cancer development and progression.