Abstract
DNA condensation is a ubiquitous phenomenon in biology, yet the physical basis for it has remained elusive. Here, we have explored the mechanism of DNA condensation through the protamine-DNA interaction, and by examining on it the influence of DNA binding drugs. We observed that the DNA condensation is accompanied by B to Ψ-DNA transition as a result of DNA base pair distortions due to protamine binding, bringing about the formation of toroidal structure through coil-globule transition. The binding energetics suggested that electrostatic energy, bending energy and hydration energy must play crucial roles in DNA condensation. EtBr intercalation interferes with the protamine-DNA interaction, challenging the distortion of the DNA helix and separation of DNA base pairs by protamine. Thus, EtBr, by competing directly with protamine, resists the phenomenon of DNA condensation. On the contrary, netropsin impedes the DNA condensation by an allosteric mechanism, by resisting the probable DNA major groove bending by protamine. In summary, we demonstrate that drugs with distinct binding modes use different mechanism to interfere with DNA condensation.
Highlights
DNA condensation is a ubiquitous phenomenon in biology, yet the physical basis for it has remained elusive
These results are well supported by recent experiments on the physical basis of why arginines are preferred over lysines in a protamine sequence[17]
In the first part of this paper, our system resorts to experiments using isothermal titration calorimetry (ITC) to elucidate the energetic factors in protamine induced DNA condensation, supported by various
Summary
DNA condensation is a ubiquitous phenomenon in biology, yet the physical basis for it has remained elusive. Drugs with clinical significance need to access specific gene sequences embedded in the compact DNA in order to realize their therapeutic role How these drugs affect the DNA condensed states will have great implications in how they regulate biological processes. The importance of Arg in the protamine induced DNA condensation was first recognized by investigating the effect of the neutral and negatively charged amino acids[16]. These results are well supported by recent experiments on the physical basis of why arginines are preferred over lysines in a protamine sequence[17]. A detailed biophysical characterization of the effect of DBD on DNA condensation will help to gain insights into the therapeutic value of drugs and to improve our understanding about the mechanism that DNA adopts in condensation
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