Human telomeric C-strand tetraplexes.

Telomeric C-strand sequences form non-Watson-Crick base-paired structures in supercoiled plasmids and in oligonucleotides at low pH. Here we examine oligonucleotides composed of 2 or 4 repeats of the human telomeric C-strand sequence d(CCCTAA)n. At low pH, the 2-repeat molecule forms a dimer which exhibits H1'-H1' nuclear Overhauser effects (NOEs) between stacked CC+ base pairs. These NOEs are characteristic of the i-motif, which is a tetraplex composed of two intercalated CC+ duplexes. The 4-repeat molecule forms an intramolecular monomeric structure at low pH, suggesting that four contiguous cytosine tracts fold into a CC+ intercalated tetraplex. These unusual structures may be relevant to the formation of guanine tetraplexes by complementary G-rich sequences. They may also provide a general mechanism for self-recognition by nucleic acids.