Effect of 3D structure of the genome on the DNA damage

2022-10
Akkose, Umit
Adebali, Ogun
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As Hi-C technologies have developed, attempts have been made to model the 3D structure of the genome. These tools are Chrom3D [1] and miniMDS [2], which can be used to model a 3D genome structure based on Hi-C data. There have been several studies to map UV and cisplatin-induced DNA damages on human cell lines. The effects of chromatin states in damage formation were well established. However, the effect of 3D structure of the genome on DNA damage formation remains unclear. Here we used Hi-C data from HeLa cells to produce a 3D genome model. Then we checked UV damage distribution on these created models. Moreover, we have created simulated UV damage datasets. Simulated datasets have the same nucleotide content as true reads, but they are randomly selected from input DNA sequencing. Because damage-seq reads have a certain nucleotide bias due to the damage site, by using these simulated reads we normalized the true damage signal. Hence, eliminating the nucleotide context bias. Since HeLa cells are cancer cell-line, there could be some chromosomal defects in our data that can affect our results. To eliminate such effects if there were any, we generated simulated datasets using input DNA sequencing. When we checked the damage distribution of these simulated datasets, (6-4)PP showed a decrease in damage towards the outer parts of the nucleus from its center. However, CPD damage distribution was more uniform throughout the nucleus. Furthermore, we normalized the true damage values with our new simulated datasets (from input DNA sequencing) and checked expected/observed damage ratio distribution throughout the nucleus. To the best of our knowledge there has been a single study addressing the effect of 3D genome structure on UV-induced mutagenesis [3], implying that outer regions of the genome are more likely to be damaged compared to the center region. Our observed/expected damage values also show that UV damage increases, both (6-4)PP and CPD, towards the outer regions of the nucleus.
https://hibit2022.ims.metu.edu.tr
https://hdl.handle.net/11511/101878
Graduate School of Informatics, Conference / Seminar

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Citation Formats
U. Akkose and O. Adebali, “Effect of 3D structure of the genome on the DNA damage,” Erdemli, Mersin, TÜRKİYE, 2022, p. 3086, Accessed: 00, 2023. [Online]. Available: https://hibit2022.ims.metu.edu.tr.
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