The relationships between DNA sequence, UV damage and transcription

DNA damages are an obstacle to transcription and replication. Damages block a cell`s ability to carry out its function and may lead to mutations and cell death. Ultraviolet (UV) radiation in sunlight is carcinogenic because it causes damages in DNA. The most abundant type of UV damages are pyrimidine dimers, primarily Cyclobutyl Pyrimidine dimers (CPDs), and pyrimidine (6-4) pyrimidone photoproducts [(6-4)PP]. These damages occur primarily in TT or TC di-nucleotides and are repaired by the nucleotide excision repair pathway. To study UV DNA damage formation and its repair, we employ state of the art methods that map the DNA damages and their repair at single nucleotide resolution across the human genome. Our lab’s previous studies have demonstrated that UV dimers have no obvious damage hotspots. Damage frequencies are determined primarily by the underlying sequence composition. However, damage formation is not completely random but dictated by the different sequence composition of the different genomic elements. Our work uncovers that asymmetry in dinucleotide frequencies between the transcribed and untranscribed strands of genes results in asymmetric damage distribution and influence the transcriptional response to damage.