Dynamic maps of UV damage formation and repair for the human genome

Jinchuan Hu, Ogun Adebali, Sheera Adar, Aziz Sancar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [highsensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidinepyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS-Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage.

Original languageAmerican English
Pages (from-to)6758-6763
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number26
DOIs
StatePublished - 27 Jun 2017

Keywords

  • DNA damage
  • Human genome
  • Nucleotide excision repair
  • Transcription factor
  • UV

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