Recurrent mutations are frequently associated with transcription factor (TF) binding sites (TFBS) in melanoma, but the mechanism driving mutagenesis at TFBS is unclear. Here, we use a method called CPD-seq to map the distribution of UV-induced cyclobutane pyrimidine dimers (CPDs) across the human genome at single nucleotide resolution. Our results indicate that CPD lesions are elevated at active TFBS, an effect that is primarily due to E26 transformation-specific (ETS) TFs. We show that ETS TFs induce a unique signature of CPD hotspots that are highly correlated with recurrent mutations in melanomas, despite high repair activity at these sites. ETS1 protein renders its DNA binding targets extremely susceptible to UV damage in vitro, due to binding-induced perturbations in the DNA structure that favor CPD formation. These findings define a mechanism responsible for recurrent mutations in melanoma and reveal that DNA binding by ETS TFs is inherently mutagenic in UV-exposed cells.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Medicine and Dentistry
2
3%
Neuroscience
2
3%
Other
7
11%
Unknown
18
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 80. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 August 2026.
All research outputs
#670,942
of 34,324,933 outputs
Outputs from Nature Communications
#11,187
of 82,723 outputs
Outputs of similar age
#11,027
of 372,059 outputs
Outputs of similar age from Nature Communications
#252
of 1,270 outputs
Altmetric has tracked 34,324,933 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 82,723 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 49.5. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 372,059 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 1,270 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
