Sensing Of DNA Damage, Instantly Activation of Repairing Proteins and Radio Sensitizers-A Biophysical Model

Abstract

The physical nature of mechanisms by which cells sense radiation-induced DNAstrand breaks remains to be elucidated. The fast induction of, for example, ATM kinase activity immediately after exposure to ionizing radiation, suggests that it acts at an early stage of signal transduction. Existing data indicate that ATM activation is not dependent on direct binding to strand breaks. However, some fundamental questions are still not responded to, such as: how ATM directly senses structure disruption in "relaxed" chromatin, and which factors determine the impressive speed and extent of the ATM response. Here, a biophysical model for the signaling mechanism of both the instant activation of repair proteins, and the recognition of a few DNA breaks by these proteins within the entire genome is proposed. The model allows for the calculation of an electromagnetic transient, produced by an electron coherent hopping current generated by the DNA damage, which is able to induce long-range activation (phosphorylation) of repair proteins almost instantly. Existing experimental evidence verifying this approach is discussed. The possible role of this study in stimulating and orientating novel applications in medical physics, as e.g. radiotherapy, is, furthermore, addressed. Citation: Arruda-Neto JDT. Sensing of DNA damage, instantly activation of repairing proteins and radio sensitizers-a biophysical model. MOJ Proteomics Bioinform. 2015;2(5):165-169. Citation: Arruda-Neto JDT. Sensing of DNA damage, instantly activation of repairing proteins and radio sensitizers-a biophysical model. MOJ Proteomics Bioinform. 2015;2(5):165-169.