Nucleotide-Resolution Genome-Wide Mapping of Oxidative DNA Damage by Click-Code-Seq.

Single-nucleotide-resolution sequencing of DNA damage is required to decipher the complex causal link between the identity and location of DNA adducts and their biological impact. However, the low abundance and inability to specifically amplify DNA damage hinders single-nucleotide mapping of adducts within whole genomes. Despite the high biological relevance of guanine oxidation and seminal recent advances in sequencing bulky adducts, single-nucleotide-resolution whole genome mapping of oxidative damage is not yet realized. We coupled the specificity of repair enzymes with the efficiency of a click DNA ligation reaction to insert a biocompatible locator code, enabling high-throughput, nucleotide-resolution sequencing of oxidative DNA damage in a genome. We uncovered thousands of oxidation sites with distinct patterns related to transcription, chromatin architecture, and chemical oxidation potential. Click-code-seq overcomes barriers to DNA damage sequencing and provides a new approach for generating comprehensive, sequence-specific information about chemical modification patterns in whole genomes.

• Publication year

  2018

• Venue

  Journal of the American Chemical Society

• Publication date

  2018-06-26

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/jacs.8b03715PMID 29944356
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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