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Bucher, D. B.

Publications and source records attributed to Bucher, D. B..

2 recordsLinked to original sources

Selection of the Early Genetic Code by Ultraviolet Light

The DNA sequences available in the prebiotic era were the genomic building blocks of the first life forms on Earth and have therefore been a matter of intense debate.1,2 On the surface of the Early Earth, ultraviolet (UV) light is a key energy source3, which is known to damage nucleic acids4. However, a systematic study of the sequence selectivity upon UV exposure under Early Earth conditions is still missing. In this work, we quantify the UV stability of all possible canonical DNA sequences and derive information on codon appearance under UV irradiation as selection pressure. We irradiate a model system of random 8mers at 266 nm and determine its UV stability via next-generation sequencing. As a result, we obtain the formation rates of the dominant dimer lesions as a function of their neighboring sequences and find a strong sequence selectivity. On the basis of our experimental results, we simulate the photodamage of short proto-genomes of 150 bases length by a Monte Carlo approach. Our results strongly argue for UV compatibility of early life and allow the ranking of codon evolutionary models with respect to their UV resistance.

biophysics↗

Sequence Dependent UV Damage of Complete Pools of Oligonucleotides

Understanding the sequence-dependent DNA damage formation requires to probe 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 with ultraviolet radiation at 266 nm and doses of up to 500 photons per base. At the dimer level our results confirm existing literature values, 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 to predict their survival chances in high-UV environments.

biophysics↗