Effect of quadruplex conformation on radiation-induced formation of 8-hydroxyguanine and unaltered base release in...

The ability of guanine-rich sequences to form quadruplex structures in telomeres for example is important in a number of biological processes such as aging, carcinogenesis and gene regulation. Ionizing radiation can cause damage to guanine moieties that can affect the stability or formation of the guanine quadruplex structures. In addition, the mechanisms of formation of these radiation damages in quadruplex structures may be different from those that occur in single- or double-stranded conformations. We have studied the quantitative aspects of the radiation induced formation of 8-hydroxy-2'-guanine base modifications and unaltered guanine base release in single-, double- and four-stranded conformations of polyriboguanylic acid as a model of guanine-rich sequences in telomere-like structures. The results show that the strandedness of guanine-rich sequences is an important variable in the observed yields of these base damages and suggests that telomere-like structures with G-quadruplexes will be relatively more radiosensitive than the other regions of duplex DNA. Hydroxyl radicals are the major reactive species that produce the DNA damage, although the presence of oxygen significantly reduces their radiation yields for all conformations of polyriboguanylic acid and changes the proportions of the yields of the various damages among the polymer conformations.