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

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Huang, Yanchao
- Other Affiliation: Shanghai Medical College of Fudan University
Azgari, Cem
- Other Affiliation: Sabanci University
Yin, Mengdie
- Other Affiliation: Shanghai Medical College of Fudan University
Chiou, Yi-Ying
- Other Affiliation: National Chung Hsing University
Lindsey-Boltz, Laura A.
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Sancar, Aziz
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Hu, Jinchuan
- Other Affiliation: Shanghai Medical College of Fudan University
Adebali, Ogun
- Other Affiliation: Sabanci University

Abstract

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.

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