2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions

• Published in: Nature communications 2021-05, Vol.12 (1), p.3018-3018, Article 3018
• Main Authors: Szabla, Rafał, Zdrowowicz, Magdalena, Spisz, Paulina, Green, Nicholas J., Stadlbauer, Petr, Kruse, Holger, Šponer, Jiří, Rak, Janusz
• Format: Article
• Language: English
• Subjects: 119/118; 140/131; 140/58; 2-Aminopurine - analogs & derivatives; 2-Aminopurine - pharmacology; 639/638/439/944; 639/638/440/947; 639/638/904; Adenine; Cyclobutane; Cyclobutane pyrimidine dimers; Deoxyribonucleic acid; Dimers; DNA; DNA - drug effects; DNA - radiation effects; DNA biosynthesis; DNA repair; DNA Repair - drug effects; Humanities and Social Sciences; Irradiation; Isomers; Molecular Dynamics Simulation; multidisciplinary; Nucleic Acids; Nucleotides; Oligomers; Prebiotics; Pyrimidine Dimers; Repair; Ribonucleic acid; RNA; RNA - chemistry; Science; Science (multidisciplinary); Substitution reactions; Transcription; Ultraviolet radiation; Ultraviolet Rays - adverse effects
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23300-y

High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments. UV-induced photodamage that likely occurred during the prebiotic synthesis of DNA and RNA is still an untackled issue for their origin on early Earth. Here, the authors show that substitution of 2,6-diaminopurine for adenine enables repair of cyclobutane pyrimidine dimers with high yields, and demonstrate that both 2,6-diaminopurine and adenine nucleosides can be formed under the same prebiotic conditions.