LPMf was shown to alter the functions of the immune system cells by inducing expression of oncogenes, affecting several factors participating in signal transduction proteins, transcription, and the apoptotic process. M. fermentans was shown to inhibit the apoptosis process induced by tumor Doxorubicin supply necrosis factor a . All these led to the assumption that infection of tumor cells by Mycoplasma may affect the activity and expression of essential nuclear enzymes such as topoisomerases, which are the targets of several anti-cancer drugs and thus interfere with the anti-cancer efficacy of these drugs. DNA topoisomerases are a family of essential nuclear enzymes that are responsible for controlling the topological state of the DNA molecules. They participate in most DNA transactions such as replication, transcription, recombination, and chromatin remodeling. DNA topoisomerases are classified as either type I or type II. Both enzyme types are further categorized into subgroups according to structural and functional features. Members of each family of enzymes are distinct in sequence, structure, and functions. The catalytic activity of DNA topoisomerases involves the formation of transient covalent bridges of enzyme-DNA SCH772984 in vivo complexes. A tyrosyl group in the active site of the enzyme attacks a phosphodiester bond on the DNA backbone and remains covalently attached to one side of the break, leaving an opposite free hydroxyl end that allows the religation step, after DNA topology is resolved, by a second nucleophilic attack of the covalent enzyme-DNA phosphotyrosine bond, releasing the enzyme for the next catalytic cycle. The involvement of these enzymes in essential cellular processes tagged topoisomerases as important targets for anti-cancer treatments and for the development of potent, more effective, anticancer drugs. The cytotoxicity of Topoisomerases inhibitors such as Camptothecin and its derivatives TPT and CPT-11, stems from their ability to stabilize the cleavable complex of Topo�CDNA, which introduces single and double strand breaks in the DNA. Topoisomerase activity is influenced by several post-translational modifications, among them phosphorylation, poly-ADP-ribosylation, and ubiquitination. Recent work done in our laboratory demonstrated the OGlcNAcylation of Topo IB, which affects its activity. The phosphorylation of DNA topoisomerase I by casein kinase II and protein kinase C up-regulate the enzyme DNA relaxation activity, whereas dephosphorylation by alkaline phosphatase inhibited this activity. In addition, poly-ADP ribosylation by poly-ADP ribose polymerase of the enzyme protein was found to down-regulate its activity. PARP-1 is known to be activated by DNA breaks; however recently, it was reported that PARP-1 can be activated by phosphorylated ERK2 in the absence of stress conditions or DNA damage.