Abstract

Bulky DNA adducts are formed by UV irradiation in melanoma. If these adducts are not repaired, they can lead to the formation of mutations that may contribute to tumour growth and progression. UV-induced damage is uniform throughout the human genome but formation and repair of UV-induced DNA damage in human cells are affected by cellular context. Mapping bulky adduct (CPDs and 6-4 photoproducts) damage from UV irradiated cellular and naked DNA revealed that accommodating the binding of proteins involved in transcription, regulation, replication and repair may induce conformational changes in the DNA making the region either more or less susceptible to the formation of bulky DNA adducts and affecting repair efficiency at DNA binding sites. The effect of transcription factor binding on bulky adducts varies, depending on the specific transcription factor, damage type and strand. On the other hand, repair is affected by chromatin states, transcription, and transcription factor binding, depending on the type of DNA damage.