ИСТИНА

G-quadruplexes (G4s) are a unique class of stable four-stranded noncanonical DNAs that play a key role in cellular processes. Here we have focused on the G4-forming 68-nt promoter region of the human telomerase reverse transcriptase (hTERT) oncogene. hTERT is the catalytic subunit of telomerase, an enzyme primarily responsible for the immortality of cancer cells. Genetic studies have identified point mutations in the hTERT promoter sequence that are directly associated with increased hTERT expression. Also known is the ability of G4s to modulate the exposure of some DNA promoter sites to various repair systems, thus influencing their efficiency. It was shown that G4s have a diverse effect on the functioning of the base and nucleotide excision repair systems. We focused on studying the impact of hTERT G4s, including altered forms of quadruplex structures, on the functioning of various DNA mismatch repair (MMR) pathways. It has been shown for the first time that MutS and MutL proteins from MMR system effectively interact with three tandem parallel quadruplexes of the G-rich strand of hTERT promoter despite single nucleotide substitutions in it. Formation of G4 in the hTERT promoter prevents the introduction of a nick by the MutL from Neisseria gonorrhoeae, thereby suppressing MMR.