High‐resolution Maps of Genome‐wide Human Damage and Repair

Abstract

Our DNA is continually damaged by cellular and environmental factors. Some of the most common mutagens, including ultraviolet light and platinum‐based drugs, cause bulky adduct formation; these are almost exclusively corrected through nucleotide excision repair. Although the basic mechanisms of excision repair are reasonably well understood, it was previously not known which genomic loci are preferentially damaged and repaired. Using the novel technologies, Damage‐seq and XR‐seq, we were able to decipher the genome‐wide kinetics of damage formation and excision repair following ultraviolet irradiation and cisplatin treatments. The single‐nucleotide resolution maps revealed cellular components affecting the DNA damage formation and repair. Despite some local exceptions, the overall damage formation profiles at initial time points exhibited a uniformity. However, the heterogenous repair resulted in an imbalanced distribution of the remaining damages after time. The repair bias is mostly caused by the transcription‐coupled repair as well as the chromatin structure of the DNA.Support or Funding InformationNational Institutes of Health Grants GM118102 and ES027255.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.