Author:
Kufner Corinna L.,Krebs Stefan,Fischaleck Marlis,Philippou-Massier Julia,Blum Helmut,Bucher Dominik B.,Braun Dieter,Zinth Wolfgang,Mast Christof B.
Abstract
AbstractUnderstanding the sequence-dependent DNA damage formation requires probing a complete pool of sequences over a wide dose range of the damage-causing exposure. We used high throughput sequencing to simultaneously obtain the dose dependence and quantum yields for oligonucleotide damages for all possible 4096 DNA sequences with hexamer length. We exposed the DNA to ultraviolet radiation at 266 nm and doses of up to 500 absorbed photons per base. At the dimer level, our results confirm existing literature values of photodamage, whereas we now quantified the susceptibility of sequence motifs to UV irradiation up to previously inaccessible polymer lengths. This revealed the protective effect of the sequence context in preventing the formation of UV-lesions. For example, the rate to form dipyrimidine lesions is strongly reduced by nearby guanine bases. Our results provide a complete picture of the sensitivity of oligonucleotides to UV irradiation and allow us to predict their abundance in high-UV environments.
Funder
Simons Foundation
Volkswagen Foundation
European Research Council
Deutsche Forschungsgemeinschaft
Center for NanoScience, Ludwig-Maximilians-Universität München
Ludwig-Maximilians-Universität München
Publisher
Springer Science and Business Media LLC
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