AttoDNA · how electronic motions affect the photostability of the genomic material

AttoDNA: how electronic motions affect the photostability of the genomic material

The goal of AttoDNA is to understand from a molecular standpoint the origins of the intrinsic photostability displayed by the canonical DNA/RNA nucleobases, which comprise our genetic lexicon. Photostability has been recently recognised as one of the main properties thought to play a crucial role in the selection of the nucleobase monomers in prebiotic extreme UV exposure, by encoding the genome using the most suitable (photostable) building blocks as an elegant solution to aid in its photo-protective design and thus defend itself against the threat of photochemical damage. An in-depth knowledge of this outstanding property also provides a unique perspective on the events where these photo-protection mechanisms fail, namely the photo-damage instances. This has direct societal connotations as it comprises the early molecular events behind the formation of skin cancer melanoma, but is also essential to understand the subsequent repair mechanisms mediated by electron transfers as those put in place by enzymes and/or in specific non-invasive treatments like photodynamic therapies, the most widespread treatment for cancer. The overall objective of the project is to find the basic physical principles shared by all DNA bases that explain this photostability, and in the long term uncover how this property modulates DNA damage and has thus an impact in mutation rates and related diseases. This overall goal is split in a series of more specific tasks, which are: - The development of a methodology that allows us to compare the theoretical models proposed face-to-face with experimental evidence for its unambiguous validation - The study of UV-light based processes in DNA/RNA nucleobases, particularly focusing for the first time in the very early events corresponding to the electronic motion prior to nuclear rearrangement - The study of ionising radiation events in DNA/RNA systems, which were unfeasible experimentally until now but that have become possible thanks to the advent of high-energy radiation sources like x-ray free electron laser (XFEL) facilities AttoDNA has concluded that very short timescales (where electron dynamics occur) may play a more important role than initially thought, and is currently exploring how this may have influenced canonical DNA bases to be chosen during evolution over structurally similar non-canonical analogues. This is being explored coupled with UV-light radiation, and has been more thoroughly assessed with VUV and higher energy regimes, which are readily measurable in XFEL facilities and that provide a unique tool to monitor ultrafast events at the electronic timescale.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз