Dynamic Maps of UV Damage Formation and Repair for the Human Genome

UV-induced DNA damage is the major carcinogen of skin cancer. We developed HS-Damage-seq to map UV damage with unprecedented sensitivity and resolution in human cells. While the distribution of UV-induced damage are mainly determined by sequence context and essentially uniform throughout the genome, transcription factors can affect damage formation at specific positions. With time-course experiments, we observed changes in damage distribution at particular genomic loci and chromatin states, which reflects the nucleotide excision repair preferences and complements the repair maps by XR-seq. Our results demonstrated that while initial damage is uniformly distributed, they are heterogeneously repaired throughout the genome. The combination of damage and repair maps provides a holistic perspective of UV damage and repair in the human genome. Overall design: 38 samples were analyzed for (6-4)PP and CPD. Two main experiments were performed: time-course (with NHF1 cell line) and cell vs naked DNA (with GM12878 cell line). Each sample has a biological replicate. We also have control samples which are the undamaged samples and reference genome samples for two cell lines.