Physics Colloquium, Thomas Schlatholter, Quantum interactions and structural dynamics — Zernike Institute for Advanced Materials
|When:||Th 28-06-2018 16:00 - 17:00|
|Affiliation:||Quantum interactions and structural dynamics - Zernike Institute for Advanced Materials|
Molecular mechanisms underlying radiation therapy
|Date:||28 June 2018|
|Start:||15:30 (Doors open and coffee available at 16:00)|
In order to improve our understanding of the molecular mechanisms underlying radiation therapy, the interaction of energetic photons and ions with gas-phase biomolecules has been intensively studied for more than 15 years. Most of these studies, both experimental and theoretical, were limited to relatively small DNA building blocks. In 2011, parallel to a team from the SOLEIL synchrotron in Orsay, our team has done pioneering experiments that combined electrospray ionization and radiofrequency ion trapping with synchrotron and ion beamlines. The first soft X-ray ionization study of a multiply protonated oligonucleotide proved that key findings obtained with DNA building blocks, such as high stability of nucleobases and fragile nature of deoxyribose, are also found in oligonucleotides. However, the underlying mechanisms of radiation action are entirely different.
As DNA in living cells occurs in de-protonated form, our current experiments focus on oligonucleotide anions. In particular, we study interactions of soft X-rays (at the carbon, nitrogen and oxygen K-edges) and MeV carbon ions (at Bragg peak energies) with oligonucleotides of different structure. In this context the most interesting DNA structures are found in the telomeres of our DNA, which consist of repetitive TTAGGG sequences. These regions do not carry genetic information but they are known to play a crucial role not only in cancer development and therapy and in aging processes. Telomeric DNA does not have double helix structure but self-assembles into so-called G-quadruplexes. Our first results indicate that short single strands of DNA are severely damaged by both X-rays and MeV ions. More complex systems such as quadruplexes or double strands can only be damaged by ions, which is in line with the superior therapeutic benefit of proton and heavy ion therapy for the treatment of many solid tumors.
A key process in DNA damage by ionizing radiation is the migration of radiation-induced positive charges (holes). Our experiments confirm the theoretical prediction that the GGG part of telomeric DNA acts as an efficient hole trap, implying that damage is mainly induced within the GGG part. This might have important implications for the development of radiosensitizing drugs.