Characterizing the potential interplay between nucleotide excision repair and R-loops

2022-10
Kaya, Sezgi
Adebali, Ogün
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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R-loops have been a focus of interest in genomics due to their non-canonical structures and unclear roles on genomes of many organisms. While R-loops contribute to gene expression and efficient transcriptional termination, they cause genome instability under certain conditions. They are formed when an RNA anneals with its complementary DNA strand. A DNA:RNA hybrid is formed and the other strand of DNA is left single-stranded (ssDNA). To date, there was no clear knowledge on R-loops’ tendency for UV damage formation or how these DNA:RNA hybrid and ssDNA structures affect nucleotide excision repair (NER), the primary mechanism to cope with UV-induced DNA damage. Therefore, we aimed to shed light on the relationship between R-loops and UV damage occurrence and repair using Rloops' positions on human and Arabidopsis genomes, and Damage-seq and XR-seq data that provided positions of UV damages and repair events, respectively. By comparing the R-loopforming locations with damage and repair occurrences, we observed that the repair efficiency on R-loops was better than their surrounding regions. However, when ATAC-seq read count normalization eliminated the impact of R-loops being on open chromatin, lower repair efficiency on R-loop centers and 5’ regions, but higher repair efficiency on 3’ regions were observed. Because this repair profile might not be valid for each R-loop, we created heatmaps of relative repair where we could group R-loops with similar repair profiles. As a result, four different relative repair profiles were observed. We also checked the damage occurrence on R-loops and saw that in general, R-loops receive less damage than their surroundings, while there were also four different damage profiles within subgroups of Rloops. Further analysis will be conducted based on these results to explain what is behind differential repair and damage profiles on R-loops and better understand the roles of Rloops on our genomes.
https://hibit2022.ims.metu.edu.tr/
https://hdl.handle.net/11511/101935
Graduate School of Informatics, Conference / Seminar

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Citation Formats
S. Kaya and O. Adebali, “Characterizing the potential interplay between nucleotide excision repair and R-loops,” Erdemli, Mersin, TÜRKİYE, 2022, p. 3088, Accessed: 00, 2023. [Online]. Available: https://hibit2022.ims.metu.edu.tr/.
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