The interplay of 3D genome organization with UV-induced DNA damage and repair

Akköse, Ümit and Adebali, Ogün (2023) The interplay of 3D genome organization with UV-induced DNA damage and repair. Journal of Biological Chemistry, 299 (5). ISSN 0021-9258 (Print) 1083-351X (Online)

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The 3D organization of the eukaryotic genome is crucial for various cellular processes such as gene expression and epigenetic regulation, as well as for maintaining genome integrity. However, the interplay between UV-induced DNA damage and repair with the 3D structure of the genome is not well understood. Here, we used state-of-the-art Hi-C, Damage-seq, and XR-seq datasets and in silico simulations to investigate the synergistic effects of UV damage and 3D genome organization. Our findings demonstrate that the peripheral 3D organization of the genome shields the central regions of genomic DNA from UV-induced damage. Additionally, we observed that potential damage sites of pyrimidine-pyrimidone (6-4) photoproducts are more prevalent in the nucleus center, possibly indicating an evolutionary pressure against those sites at the periphery. Interestingly, we found no correlation between repair efficiency and 3D structure after 12 min of irradiation, suggesting that UV radiation alters the genome's 3D organization in a short period of time. Interestingly, however, 2 h after UV induction, we observed more efficient repair levels in the center of the nucleus relative to the periphery. These results have implications for understanding the etiology of cancer and other diseases, as the interplay between UV radiation and the 3D genome may play a role in the development of genetic mutations and genomic instability.
Item Type: Article
Uncontrolled Keywords: 3D genome; 3D genome model; cyclubutane pyrimidine dimer (CPD); Damage-seq; DNA damage; DNA repair; Hi-C sequencing; NGS simulation; nucleotide excision repair; pyrimidine sequence; pyrimidine-pyrimidone (6-4) photoproduct; shielding effect; TAD; UV; XR-seq
Divisions: Faculty of Engineering and Natural Sciences
Depositing User: Ogün Adebali
Date Deposited: 06 Aug 2023 15:18
Last Modified: 06 Aug 2023 15:18

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