This chapter presents a summary of current research efforts on the direct interaction of high energy ionizing radiation with DNA and its immediate surroundings. These interactions lead to primarily excitation and ionization events (direct effect). The direct effect is accompanied with hole (unpaired spin) and excess electron transfer from the surroundings into DNA (i.e., quasi-direct effect). The direct and quasi-direct effects are jointly called direct-type effect. Subsequent electron and hole transfer processes lead to localization of most damages to specific DNA bases. Intra-base pair proton transfer (proton transfer within DNA) and duplex-to-solvent proton transfer (proton transfer to the surrounding medium) limit these hole and electron transfer processes. DNA radicals (cationic, anionic and neutral) formed via direct-type effects alone or combined with excited states are found to be responsible for the sugar radicals that are associated with radiation-produced strand breaks. Also, this review presents a summary of low energy electron-mediated production of DNA damage by dissociative electron attachment. This chapter also illustrates the difference between the mechanisms of radiation effects and radiation-induced chemistry of DNA and its components occurring after high linear energy transfer ion-beam irradiation from those after low linear energy transfer irradiation.