Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene

Wentao Li, Jinchuan Hu, Ogun Adebali, Sheera Adar, Yanyan Yang, Yi Ying Chiou, Aziz Sancar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. BaP forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method for capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors, and after damage-specific immunoprecipitation, the adaptor-ligated oligonucleotides are converted to dsDNAwith an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps. We have termed this method translesion excision repair-sequencing (tXR-seq). In contrast to our previously described XR-seq method, tXR-seq does not depend on repair/removal of the damage in the excised oligonucleotides, and thus it is applicable to essentially all DNA damages processed by nucleotide excision repair. Here we present the excision repair maps for CPDs and BPDE-dG adducts generated by tXR-Seq for the human genome. In addition, we report the sequence specificity of BPDE-dG excision repair using tXR-seq.

Original languageAmerican English
Pages (from-to)6752-6757
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number26
DOIs
StatePublished - 27 Jun 2017

Bibliographical note

Funding Information:
This work was supported by NIH Grants GM118102 and ES027255.

Keywords

  • Benzo[a]pyrene diol epoxide
  • Lung cancer
  • Nucleotide excision repair
  • Txr-seq
  • Uv

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