Ionizing radiation (IR) can cause damage to DNA molecules, both through direct ionization and through induction of oxidative stress. Thus the resistance and the rescue to radiation-induced damage are mostly associated with the efficacy of DNA repair system, which involves different types of enzymes and signal molecules, many of which are not yet identified. These enzymes represent target for molecules that, modulating their activity, may increase or decrease the efficiency of radiation-induced DNA repair and consequently cell viability. Topoisomerases (Tops) are ubiquitous and essential enzymes that solve the DNA topological problems deriving from replication, transcription, chromatin assembly, recombination, and chromosome segregation by introducing transient breaks into the helix. Human Topoisomerase IB (Top IB) is also of significant medical interest being the selective target of antitumor drugs such as camptothecin and its water-soluble derivatives, widely used for treating cancers sometimes in association with radiotherapy. There are several evidences that Top IB is involved in DNA repair, although contradicting results have been reported. The role of Top IB in repairing DNA damage induced by X rays was studied on two human cancer cell lines (i.e. colorectalcarcinoma - HCT 116 - and adenocarcinoma - HT 29) evaluating the relation between Top IB activity and the level of DNA damage. After IR exposure, the DNA repair is correlated to an increase of Top IB activity but not of its synthesis. Based on these outcomes and on the available literature, we figure that the radiation exposure induces a post-translational modification of the enzyme modulating its activity. Our future prospective is to identify these post-translational modifications, and also to find out relation between Top IB and other repair proteins. These results provide a new insight into the mechanisms for genomic integrity maintenance, and could also contribute to new strategies in cancer treatment.
Jahan, Z., Cerreto, M., Aversa, G., Rufini, S., Desideri, A., Giovanetti, A. (2015). Role of topoisomerase IB on damage induced by ionizing radiation. In K P Mishra Editor (a cura di), Biological Responses, Monitoring and Protection from Radiation Exposure (pp. 193-206). Hauppauge NY 11788-3619 : Nova Science Publishers, Inc..
Role of topoisomerase IB on damage induced by ionizing radiation
RUFINI, STEFANO;DESIDERI, ALESSANDRO;
2015-01-01
Abstract
Ionizing radiation (IR) can cause damage to DNA molecules, both through direct ionization and through induction of oxidative stress. Thus the resistance and the rescue to radiation-induced damage are mostly associated with the efficacy of DNA repair system, which involves different types of enzymes and signal molecules, many of which are not yet identified. These enzymes represent target for molecules that, modulating their activity, may increase or decrease the efficiency of radiation-induced DNA repair and consequently cell viability. Topoisomerases (Tops) are ubiquitous and essential enzymes that solve the DNA topological problems deriving from replication, transcription, chromatin assembly, recombination, and chromosome segregation by introducing transient breaks into the helix. Human Topoisomerase IB (Top IB) is also of significant medical interest being the selective target of antitumor drugs such as camptothecin and its water-soluble derivatives, widely used for treating cancers sometimes in association with radiotherapy. There are several evidences that Top IB is involved in DNA repair, although contradicting results have been reported. The role of Top IB in repairing DNA damage induced by X rays was studied on two human cancer cell lines (i.e. colorectalcarcinoma - HCT 116 - and adenocarcinoma - HT 29) evaluating the relation between Top IB activity and the level of DNA damage. After IR exposure, the DNA repair is correlated to an increase of Top IB activity but not of its synthesis. Based on these outcomes and on the available literature, we figure that the radiation exposure induces a post-translational modification of the enzyme modulating its activity. Our future prospective is to identify these post-translational modifications, and also to find out relation between Top IB and other repair proteins. These results provide a new insight into the mechanisms for genomic integrity maintenance, and could also contribute to new strategies in cancer treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
