Cargando…
Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin
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 impor...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013872/ https://www.ncbi.nlm.nih.gov/pubmed/36853943 http://dx.doi.org/10.1073/pnas.2216907120 |
_version_ | 1784906872189353984 |
---|---|
author | Bohm, Kaitlynne A. Morledge-Hampton, Benjamin Stevison, Scott Mao, Peng Roberts, Steven A. Wyrick, John J. |
author_facet | Bohm, Kaitlynne A. Morledge-Hampton, Benjamin Stevison, Scott Mao, Peng Roberts, Steven A. Wyrick, John J. |
author_sort | Bohm, Kaitlynne A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10013872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-100138722023-08-28 Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin Bohm, Kaitlynne A. Morledge-Hampton, Benjamin Stevison, Scott Mao, Peng Roberts, Steven A. Wyrick, John J. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-02-28 2023-03-07 /pmc/articles/PMC10013872/ /pubmed/36853943 http://dx.doi.org/10.1073/pnas.2216907120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Bohm, Kaitlynne A. Morledge-Hampton, Benjamin Stevison, Scott Mao, Peng Roberts, Steven A. Wyrick, John J. Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title | Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title_full | Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title_fullStr | Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title_full_unstemmed | Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title_short | Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
title_sort | genome-wide maps of rare and atypical uv photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013872/ https://www.ncbi.nlm.nih.gov/pubmed/36853943 http://dx.doi.org/10.1073/pnas.2216907120 |
work_keys_str_mv | AT bohmkaitlynnea genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin AT morledgehamptonbenjamin genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin AT stevisonscott genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin AT maopeng genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin AT robertsstevena genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin AT wyrickjohnj genomewidemapsofrareandatypicaluvphotoproductsrevealdistinctpatternsofdamageformationandmutagenesisinyeastchromatin |