The Relationship Between 3d Genome Organization And Uv-Induced Dna Damage And Repair

Official URL: https://risc01.sabanciuniv.edu/record=b3205744

The three-dimensional (3D) configuration of the eukaryotic genome is essential for myriad cellular processes, such as the modulation of gene expression and the orchestration of epigenetic regulation, as well as the preservation of genome integrity. Nonetheless, understanding interaction between UV-induced DNA damage and subsequent repair mechanisms, and their connection with the genome’s 3D structure remains underexplored. In the present study, we harness Hi-C, Damage-seq, and XR-seq datasets, complemented by in silico simulations, to look into the interconnection between UV damage and the 3D genome organization. Our findings reveals that the genome’s peripheral 3D configuration acts as a defensive barrier, safeguarding the central genomic DNA sectors from UV-induced damage. Furthermore, we found that potential damage sites of pyrimidine-pyrimidone (6-4) photoproducts appear with a higher frequency in the nucleus center, possibly suggesting an evolutionary selection pressure working against the formation of these sites at the genome periphery. We did not find any correlation between the effectiveness of DNA repair and the 3D structure of the genome 12 minutes after UV radiation, showing that UV radiation changes the 3D organization of the genome in a relatively short time frame. Surprisingly, two hours after UV induction, we detected more proficient repair activity in the nucleus center relative to its periphery. Our results provide valuable insights for the understanding of the etiology of cancer and other diseases. The interplay between UV radiation and the 3D organization of the genome may contribute significantly to the emergence of genetic mutations and genomic instability