Effects of replication domains on genomewide UV-induced DNA damage and repair

Huang, Yanchao and Azgari, Cem and Yin, Mengdie and Chiou, Yi Ying and Lindsey-Boltz, Laura A. and Sancar, Aziz and Hu, Jinchuan and Adebali, Ogün (2022) Effects of replication domains on genomewide UV-induced DNA damage and repair. PLoS Genetics, 18 (9). ISSN 1553-7390 (Print) 1553-7404 (Online)

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Nucleotide excision repair is the primary repair mechanism that removes UV-induced DNA lesions in placentals. Unrepaired UV-induced lesions could result in mutations during DNA replication. Although the mutagenesis of pyrimidine dimers is reasonably well understood, the direct effects of replication fork progression on nucleotide excision repair are yet to be clarified. Here, we applied Damage-seq and XR-seq techniques and generated replication maps in synchronized UV-treated HeLa cells. The results suggest that ongoing replication stimulates local repair in both early and late replication domains. Additionally, it was revealed that lesions on lagging strand templates are repaired slower in late replication domains, which is probably due to the imbalanced sequence context. Asymmetric relative repair is in line with the strand bias of melanoma mutations, suggesting a role of exogenous damage, repair, and replication in mutational strand asymmetry.
Item Type: Article
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Ogün Adebali
Date Deposited: 26 Mar 2023 16:34
Last Modified: 26 Mar 2023 16:34
URI: https://research.sabanciuniv.edu/id/eprint/45126

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