2022 Annual Meeting Report: Let’s Take a Closer Look! Can the Resolution Achieved with Genome-Wide Mapping of DNA Damage Advance Toxicology?

By Sarah Carratt posted 04-05-2022 13:27


Traditionally, measurement of DNA adduct formation and DNA damage has been used to understand chemical exposures and xenobiotic metabolism. In her 2022 EUROTOX Bo Holmstedt Memorial Award Lecture, delivered during the 2022 SOT Annual Meeting and ToxExpo, Dr. Shana Sturla asked if quantification of DNA damage can be used in a predictive way, and described how understanding the distribution of DNA damage across the genome has the potential to help us better predict etiologies of carcinogenic mutations and other biological processes driven by genomic instability.

Two critical definitions used in Dr. Sturla’s lecture are damage signature (genome-wide map of chemically induced DNA damage) and mutational signature (genome-wide map of genetic sequence changes). Advances in sequencing technologies and data analysis pipelines have allowed for damage signatures to be described at the single nucleotide level.

By coupling different next-generation sequencing technologies, Dr. Sturla and others in the field are aligning mutational signatures with damage signatures to understand complex relationships between chemical exposures and genetic characteristics. This field of study and the emerging technologies have exciting implications for our ability to understand disease-initiating events and predict toxicities.

To end on a personal note: Toxicology is a very broad field and sometimes the scientific presentations at SOT can be highly technical and/or geared toward an expert/niche audience. When I write these reports, I typically try to make sure I provide enough information to make the more difficult concepts accessible, including key definitions at the end of the blog post. I included a long list of definitions in this post, but in this case, I actually think this list is redundant. Dr. Sturla is an extremely clear science communicator and her presentation has exceptional graphics. It’s still a highly technical presentation, but if you are at all interested in this topic—even if it’s not in your area of expertise—I highly recommend watching the recording of this talk.

Loved the talk and want to know more? Check out this excellent review on next-generation DNA damage sequencing by Mingard et al. (2020):

Key Term


OG, 8-oxoG, 8-oxodG

An oxidized derivative of deoxyguanosine; a major product of DNA oxidation

Abasic site


Also: apurinic/apyrimidinic site; a location in DNA that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage


Used to identify abasic (AP) sites genome-wide

Apurinic/apyrimidinic site


Also: Abasic site; a location in DNA that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage

Base excision repair


Process of DNA repair during which a DNA glycosylase recognizes and removes the damaged base, leaving an abasic site that is further processed by enzymes that restore the correct base; corrects DNA damage from oxidation, deamination, and alkylation



A well-studied pro-carcinogen that is metabolically activated by cytochrome P450 enzymes

Bulky DNA adducts

Markers of exposure to genotoxic aromatic compounds, which reflect an individual’s ability to metabolically activate carcinogens and to repair DNA damage


A method used to analyze protein interactions with DNA

Chromatin immunoprecipitation


An antibody-based technology used to selectively enrich specific DNA-binding proteins along with their DNA targets


Used to identify genome-wide cisplatin crosslinking sites at base resolution


Used for genome-wide mapping of oxidative DNA damage


Used for genome-wide mapping of UV-induced DNA damage

Cyclobutane pyrimidine dimer


A type of UV-induced helix-distorting DNA damage

DNA damage signature

A genome-wide map of chemically induced damage

DNA mutational signature

A genome-wide map of genetic sequence changes


Growing or originating from within an organism


A method used to map genome-wide oxidative DNA damage


The study of changes in gene activity caused by mechanisms other than DNA sequence changes: DNA methylation, DNA-protein interactions, chromatin accessibility, histone modifications


A method used to map genome-wide modifications to DNA nucleobases


Growing or originating from outside an organism

Gene expression

The process by which the information encoded in a gene is used to direct the assembly of a protein molecule; quantified by assessing levels of transcript mRNA (RT-qPCR, RNA-seq) or protein (western blot)


The complete set of genes or genetic material present in a cell or an organism


A method for genome-wide mapping of DNA replication patterns, single-strand breaks, and lesions


High sensitivity damage sequencing; used for single-nucleotide resolution damage mapping

Immunoaffinity chromatography

A method for separating target antibodies or antigens from a heterogenous solution

Massively parallel sequencing technology

A technology enabling the sequencing of many DNA strands at the same time instead of one at a time as with traditional Sanger sequencing; also called next-generation sequencing

Next-generation sequencing


A technology for determining the sequence of DNA or RNA; initially called massively parallel sequencing


A method for genome-wide mapping of DNA modifications at single-nucleotide resolution

Nucleotide excision repair


Pathway to remove bulky DNA lesions such as those formed by UV light, environmental mutagens, and some cancer chemotherapeutic adducts from DNA


A method for genome-wide mapping of 8-oxodG locations


A method for genome-wide mapping of ribonucleotides in genomic DNA; polymerase usage sequencing

Reactive oxygen species


A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell

Ribonucleotide excision repair


Pathway to remove mis-incorporated ribonucleotides from DNA


Nucleotide containing ribose as its pentose component; incorporated into the DNA as primers for lagging strand synthesis, after which they are removed by an exonucleolytic action


A method for genome-wide mapping of ribonucleotides in genomic DNA


A method for quantification of mRNA in a biological sample using next-generation sequencing; allows for assessment of differential gene expression

Sanger sequencing

A method for determining the nucleotide sequence of DNA; also known as the chain termination method

Single nucleotide polymorphisms


A single base-pair difference in the DNA sequence


A method for genome-wide mapping of in vivo DNA single-strand breaks (SSBs)


A method for genome-wide mapping of single-strand breaks (SSBs) at the nucleotide level

Transcription factor


A protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence


The sum total of all the messenger RNA molecules expressed from the genes of an organism

Translesion DNA synthesis


Process by which specialized DNA polymerases can bypass DNA damage to replicate DNA


A method for genome-wide mapping of nucleotide excision repair

This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.

On-demand recordings of all Featured and Scientific Sessions delivered during the 2022 SOT Annual Meeting and ToxExpo will be available to meeting registrants in the SOT Event App and Online Planner after their conclusion, through July 31, 2022.