02/11/2023
A graphic in which rays are refracted and fall on a target.

X-rays interact with Gene-V Protein and Ectoine.

Source: Royal Society of Chemistry (Back cover Physical Chemistry Chemical Physics (PCCP), Issue7, 2023, Creative Commons)

The maintenance of DNA – as the carrier of genetic information – is crucial for the survival of cells. As soon as damage occurs to the DNA for example due to chemical attacks or radiation exposure, repair processes are initiated. Single-stranded DNA-binding proteins such as Gene-V Protein (G5P) are important components of DNA repair. By binding to the delicate single-stranded DNA, they can protect it from damage until full biological mechanisms are completed. But how does the G5P itself react to ionizing radiation, e.g., when radiation treatment is carried out during cancer therapy?

In this study, a new approach to extend the possible irradiation time of the protein G5P was investigated. For this purpose, a (radical) scavenger was used during small-angle X-ray scattering (SAXS) of the DNA-binding protein. The molecule ectoine was used as a cosolute (an additional solute) and as a scavenger to protect the G5P protein from radicals generated during radiation exposure. The radiation-induced changes in G5P were monitored during the SAXS measurements and the resulting energy-damage relation was determined from microdosimetric calculations using Monte Carlo-based particle scattering simulations. In the presence of ectoine, a threefold increase in energy deposition was required to achieve the same damage level as in pure G5P solutions. This indicates that ectoine increases the potential radiation exposure time by interacting with reactive species in aqueous solution before radiation damage to G5P is observed. In addition, the dominant mode of damage shifted from G5P aggregation in absence of ectoine towards G5P fragmentation for solutions containing ectoine as a cosolute. This could be related to the preferential exclusion of the cosolute from the protein surface. Therefore, it was shown that ectoine offers a possibility to improve the structure determination of proteins via Bio-SAXS in future studies and thus can be used as a radiation protection of DNA-binding proteins.

Bio-SAXS of single-stranded DNA-binding proteins: radiation protection by the compatible solute ectoine
Dorothea C. Hallier, Glen J. Smales, Harald Seitz, Marc Benjamin Hahn
published in: Physical chemistry chemical physics (PCCP), Volume 25, Issue 7, Pages 5,372 bis 5,382

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