MMR2 Activators

MMR2, as an integral component of the DNA mismatch repair system, is activated by a variety of chemical compounds that instigate or exacerbate DNA damage, thereby necessitating repair. Cisplatin, for example, is known to form DNA adducts that MMR2 recognizes and binds to, which enhances its activity as part of the DNA mismatch repair pathway. Similarly, Methoxyamine, by targeting the base excision repair pathway, increases the load of DNA lesions, which can indirectly enhance MMR2's activity. The accumulation of single-strand breaks caused by PARP inhibitors such as Olaparib and Talazoparib serves as substrates for MMR2, thereby enhancing its functional activity in the repair process. Additionally, Etoposide, a topoisomerase II inhibitor, and Trabectedin, which alkylates DNA, both contribute to an increase in DNA double-strand breaks and structural aberrations, respectively, thus indirectly increasing the functional demand on MMR2.

Other chemicals, such as N6-furfuryladenine, also known as kinetin, enhance MMR2 function by increasing the demand for DNA repair mechanisms within the cell. Mirin, an MRE11 inhibitor, and Aphidicolin, a DNA polymerase inhibitor, create conditions that lead to an increased requirement for MMR2-mediated mismatch repair by impeding DNA double-strand break repair and causing stalled replication forks, respectively. Hydroxyurea, by inhibiting ribonucleotide reductase, causes replication stress, which may lead to DNA mismatches and subsequent activation of MMR2. Lastly, Mitomycin C crosslinks DNA strands, creating complex lesions that are recognized by the mismatch repair machinery, thereby enhancing the activity of MMR2 in response to this form of DNA damage. Collectively, these activators of MMR2, through their targeted effects on DNA integrity, necessitate the heightened function of MMR2 in maintaining genomic stability.