Single nucleotide-resolution mapping of UVB irradiation-induced cyclobutane pyrimidine dimers. Homo sapiens

The most prevalent type of DNA damage induced by ultraviolet B (UVB) radiation is the cyclobutane pyrimidine dimer (CPD), which is the principal DNA lesion associated with UV mutagenesis and induction of skin cancer. The distribution of CPDs is heterogeneous across the mammalian genome but so far has been mapped only by low-resolution techniques or within a few specific genes. Here we present an experimental approach, which is able to derive nucleotide resolution level data for CPD distribution at dipyrimidine positions in human UVB-irradiated cells and identify clusters of UVB-derived damage positions. We tested and validated our method with irradiated and non-irradiated fibroblast cells as well as with irradiated naked DNA and were able to infer selective genome-wide profiles as well as specific motif elements susceptible to UVB damage. Our method is suitable for genome-wide mapping of DNA damage in cells and under different experimental conditions, with a specificity and resolution not achievable by other current techniques.