Skip to main navigation Skip to search Skip to main content

Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin

  • Kaitlynne A. Bohm
  • , Benjamin Morledge-Hampton
  • , Scott Stevison
  • , Peng Mao
  • , Steven A. Roberts
  • , John J. Wyrick
  • Washington State University Pullman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Ultraviolet (UV) light induces different classes of mutagenic photoproducts in DNA, namely cyclobutane pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and atypical thymine–adenine photoproducts (TA-PPs). CPD formation is modulated by nucleosomes and transcription factors (TFs), which has important ramifications for Ultraviolet (UV) mutagenesis. How chromatin affects the formation of 6-4PPs and TA-PPs is unclear. Here, we use UV damage endonuclease-sequencing (UVDE-seq) to map these UV photoproducts across the yeast genome. Our results indicate that nucleosomes, the fundamental building block of chromatin, have opposing effects on photoproduct formation. Nucleosomes induce CPDs and 6-4PPs at outward rotational settings in nucleosomal DNA but suppress TA-PPs at these settings. Our data also indicate that DNA binding by different classes of yeast TFs causes lesion-specific hotspots of 6-4PPs or TA-PPs. For example, DNA binding by the TF Rap1 generally suppresses CPD and 6-4PP formation but induces a TA-PP hotspot. Finally, we show that 6-4PP formation is strongly induced at the binding sites of TATA-binding protein (TBP), which is correlated with higher mutation rates in UV-exposed yeast. These results indicate that the formation of 6-4PPs and TA-PPs is modulated by chromatin differently than CPDs and that this may have important implications for UV mutagenesis.

Original languageEnglish
Article numbere2216907120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number10
DOIs
StatePublished - Mar 7 2023

Keywords

  • 6-4 photoproducts
  • TA photoproduct
  • nucleosome
  • thymine–adenine photoproduct
  • transcription factor binding site

Fingerprint

Dive into the research topics of 'Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin'. Together they form a unique fingerprint.

Cite this