Human telomeric C–strand tetraplexes

Abstract

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.

MYC and Chromatin

“…Depending on the length and nature of the guanine blocks, G4 DNA can involve either one, two, or four separate DNA strands. And if conditions are right, the displaced C-rich strand can fashion a structure known as the 'i-motif', which is a four-stranded structure composed of two intercalated, hemiprotonated, cytosine-cytosine base pairs [50]. Formation of H-and G 4 -DNA and i-motif structures could influence transcription in a number of ways, including preventing recognition by sequence-specific DNA-binding proteins, altering the distance or stereospecific alignment of promoter elements, or recruiting new factors that specifically recognize altered DNA configurations.…”

Stable loop in the crystal structure of the intercalated four-stranded cytosine-rich metazoan telomere.

“…In multicellular animals, the C-rich strand repeating sequence is generally d(TAACCC). NMR studies of C-rich telomere sequences show that they can also form a four-stranded structure with cytosine-containing parallel duplexes held together by hemiprotonated (C C+) base pairs and two duplexes intercalated with each other in opposite polarity (8)(9)(10). Recent x-ray diffraction studies of C-rich deoxynucleotides have revealed many features of this intercalative system (11,12).…”

Telomeric nucleic acids: C-strand structure and a telomerase RNA mutant

“…These C-rich oligonucleotides form stable structures at low pH (Ahmed and Henderson, 1992;Ahmed, et al, 1994). Two dimensional NMR spectroscopy showed that these structures were C-tetraplexes (Ahmed, et al, 1994). In addition, electrophoresis experiments demonstrated that C-tetraplexes, like G-tetraplexes, could mediate recognition and binding between identical nucleic acid sequences (Ahmed, et al, 1994).…”

“…We have examined the structural characteristics of oligonucleotides containing telomeric Cstrand sequences. These C-rich oligonucleotides form stable structures at low pH (Ahmed and Henderson, 1992;Ahmed, et al, 1994). Two dimensional NMR spectroscopy showed that these structures were C-tetraplexes (Ahmed, et al, 1994).…”

“…Exactly how these biologically relevant C-rich sequences are structured has yet to be determined and could involve either C G C+ triplexes or C-tetraplexes. In contrast, the C-rich strand of telomeres has recently been shown to form C-tetraplexes (Ahmed, et al, 1994). When telomeric sequences are put in supercoiled plasmids, the C-rich strand adopts an unusual structure at low pH (Lyamichev, et al, 1989;Belotserkovskii, et al, 1992;Voloshin, et al, 1992).…”