Hole transfer energetics in structurally distorted DNA: the nucleosome core particle.

The dynamics of long-range hole transport (HT) through DNA are critically dependent on the relative energies of guanine radical cation states. Electrostatic contacts with protein fragments and changes in the secondary structure of the DNA helix are expected to directly influence the stability of a guanine radical cation. This expectation is especially relevant when considering DNA HT in the eukaryotic nucleus, where DNA is condensed into nucleosome core particles (NCPs), the fundamental building blocks of chromatin. Using quantum-chemical calculations, we consider how the electrostatic interactions between the DNA nucleobases and the surrounding protein and water atoms and the structural changes in DNA arising from compaction into a NCP affect the energetics of hole transfer between guanine sites. We find that structural distortions of DNA can have dramatic consequences for the stability of a guanine radical cation, and therefore, these effects must be taken into account during the modeling of in vivo DNA HT and in the interpretation of experimental findings. When the electrostatic potential arising from the water and basic histone proteins is included we find that DNA-histone contacts, particularly between arginine residues and the DNA minor groove, destabilize the hole state on specific guanine residues. Therefore, contacts between the DNA nucleobases and basic amino acids have the potential to perturb the sites of preferred hole stability in DNA.