Guanine (G) radicals are precursors to DNA oxidative damage, correlated with carcinogenesis and aging. During the past few years, we demonstrated clearly an intriguing effect: G radicals can be generated upon direct absorption of UV radiation with energy significantly lower than the G ionization potential. Using nanosecond transient absorption spectroscopy, we studied the primary species, ejected electrons and guanine radicals, which result from photoionization of various DNA systems in aqueous solution. The DNA propensity to undergo electron detachment at low photon energies greatly depends on its secondary structure. Non-detected for monomers or unstacked oligomers, it may be one order of magnitude higher for G-quadruplexes than for duplexes. The experimental results point toward non-vertical processes, associated with the relaxation of electronic excited states. Theoretical studies are required to validate the mechanism and determine the factors that enter in play. In any case, such a mechanism, which may be operative over a broad excitation wavelength range, explains the occurrence of oxidative damage observed upon UVB and UVA irradiation. Quantification of G radical populations and their time evolution questioned some widespread views. It appeared that G radicals may be generated with the same probability as pyrimidine dimers, which are considered to be the major lesions induced upon absorption of low-energy UV radiation by DNA. As the most important part of the initially created radical cations undergoes deprotonation, the vast majority of the final reaction products is expected to stem from long-lived deprotonated radicals. Consequently, the widely used oxidation marker 8-oxodG is not representative of the extent of oxidative damage when this is triggered by generation of radical cations. Beyond the biological consequences, photo-generation of electron holes in G-quadruplexes may inspire applications in nano-electronics; although four-stranded structures are currently studied as molecular wires, their behavior as photoconductors has not been explored so far. In the present Account, after highlighting some key experimental issues, we first describe the photo-ionization process and, then, we focus on radicals. We use as show-cases new results obtained for genomic DNA and Oxytricha G-quadruplexes. Generation and reaction dynamics of G radicals in these systems provide a representative picture of the phenomena reported previously for duplexes and G-quadruplexes, respectively.