Moreover, we also demonstrated that in Mycoplasma-infected cells an increase in ADP-ribosylation of Topo I BEZ235 protein was observed. Since Topo I is the target of the camptothecins, which are potent anti-cancer agents, the enzyme modification and the reduction in its activity may influence the efficacy of this anticancer drug in tumor cells that are infected with Mycoplasma. Indeed, we demonstrate that infection of MCF7 cells with M. fermentans prior to CPT treatment significantly decreased the cytotoxic effect of CPT. However, since we previously showed that CPT inhibited Mycoplasma growth Horowitz, 1997 #55, it is also possible that the alteration in CPT efficacy is also due to the consumption of CPT by Mycoplasma. In summary, we believe that the pathway by which infection of cells with M. fermentans decreases the DNA relaxation activity of Topo I is via the induction of the MAPK signaling pathway in which ERK1/2 is phosphorylated by MEK. As illustrated in Figure 9, the p-ERK activates PARP-1, which modifies Topo I protein by ADP-ribosylation, decreasing the ability of Topoisomerase I to relax PR-171 Proteasome inhibitor supercoiled DNA. Our data also suggest that this ADP ribosylation of Topo I interfered with its ability to bind DNA as demonstrated by the diminished inhibition of Topo I by CPT treatment in Mycoplasma-infected cells. In conclusion, infection of tumor cells with Mycoplasma induced signal transduction pathways that can cause modifications of essential cellular enzymes such as Topo I and affect their activity. Moreover, the enzyme modification and the reduction in its activity influence the efficacy of its inhibitor as an anti-cancer drug. It is not yet clear if Mycoplasma infection of tumors occurs in vivo in patients, but our data clearly indicate that this possibility should be considered, specifically when anti-Topo I drugs are administered. Previous studies have attempted to explain the mechanism of ��-radiation resistance by identifying the roles of radiation-inducible genes. Some novel proteins such as Ddr and Ppr are reportedly implicated in the extreme radioresistance of D. radiodurans based on the up-regulation of these genes following irradiation and the increased susceptibility of these mutants to ��-radiation. DdrA binds to the 3�� ends of single-stranded DNA to protect them from nuclease degradation. The DdrB protein, which is a prototype of a new bacterial single-stranded DNA-binding protein family, stimulates single-stranded DNA annealing. These two proteins were recently implicated in an Extended Synthesis-Dependent Strand Annealing -mediated genome reconstitution process, which is a distinctive DNA repair system in D. radiodurans. The PprA protein binds to broken double-stranded DNA, protects it from degradation, and stimulates DNA ligase activities in vitro. However, recent research has demonstrated that PprA has pleiotropic roles by undergoing dynamic changes in its localization.