Role of human topoisomerase IB on ionizing radiation induced damage

Ionizing radiation can induce DNA strand breaks' formation both through direct ionization and through induction of oxidative stress. The resistance to radiation is mostly associated with the efficacy of DNA repair system. The ionizing radiation damage response of human topoisomerase IB, that is the selective target of camptothecin and derivatives widely used for various cancers often in association of radiotherapy, has been investigated treating with 30 Gy of X-rays a Saccharomyces cerevisiae strain in which the endogenous topoisomerase IB, not essential in this organism, has been deleted and a similar strain which overexpresses the human enzyme. The results show that before irradiation the genetic damage is significantly lower in cells containing human topoisomerase, but soon after irradiation the amount of DNA breaks in these cells is larger than in cells not containing the enzyme. Kinetic analysis of DNA repair rate as well as colonies growth demonstrate that cells containing human topoisomerase display a more efficient rescue. Finally, ionizing radiation induces in the Saccharomyces cells an increase of enzymatic activity and of the amount of the enzyme bound to the DNA indicating a direct role of topoisomerase IB in the mechanism of nucleic acid repair.