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

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 under...

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Autores principales: Akköse, Ümit, Adebali, Ogün
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192929/
https://www.ncbi.nlm.nih.gov/pubmed/37028766
http://dx.doi.org/10.1016/j.jbc.2023.104679
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author Akköse, Ümit
Adebali, Ogün
author_facet Akköse, Ümit
Adebali, Ogün
author_sort Akköse, Ümit
collection PubMed
description 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.
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spelling pubmed-101929292023-05-19 The interplay of 3D genome organization with UV-induced DNA damage and repair Akköse, Ümit Adebali, Ogün J Biol Chem JBC Communication 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. American Society for Biochemistry and Molecular Biology 2023-04-05 /pmc/articles/PMC10192929/ /pubmed/37028766 http://dx.doi.org/10.1016/j.jbc.2023.104679 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle JBC Communication
Akköse, Ümit
Adebali, Ogün
The interplay of 3D genome organization with UV-induced DNA damage and repair
title The interplay of 3D genome organization with UV-induced DNA damage and repair
title_full The interplay of 3D genome organization with UV-induced DNA damage and repair
title_fullStr The interplay of 3D genome organization with UV-induced DNA damage and repair
title_full_unstemmed The interplay of 3D genome organization with UV-induced DNA damage and repair
title_short The interplay of 3D genome organization with UV-induced DNA damage and repair
title_sort interplay of 3d genome organization with uv-induced dna damage and repair
topic JBC Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192929/
https://www.ncbi.nlm.nih.gov/pubmed/37028766
http://dx.doi.org/10.1016/j.jbc.2023.104679
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