Conformations of DNA strands containing GAGT, GACA, or GAGC tetranucleotide repeats

Abstract

The (GA)(n) microsatellite has been known from previous studies to adopt unusual, ordered, cooperatively melting secondary structures in neutral aqueous solutions containing physiological concentrations of salts, at acid pH values or in aqueous ethanol solutions. To find more about the primary structure specificity of these structures, we performed parallel comparative studies of related tetranucleotide repeats (GAGC)(5), (GAGT)(5), and (GACA)(5). The general conclusion following from these comparative studies is that the primary structure specificity is fairly high, indicating that not only guanines but also adenines play a significant role in the stabilization of these unusual structures. (GAGC)(5) is a hairpin or a duplex depending on DNA concentration. Neither acid pH nor ionic strength or the presence of ethanol changed the secondary structure of (GAGC)(5) in a significant way. (GACA)(5) forms a weakly stable hairpin in neutral aqueous solutions but forms a duplex at acid pH where cytosine is protonated. (GAGT)(5) behaves most similar to (GAGA)(5). Salt induces its hairpin to duplex transition at neutral pH and an isomerization into another, probably parallel stranded, duplex takes place at acid pH. (GAGT)(5) is the only of the three present 20-mers that responds to ethanol like (GAGA)(5).

Structural polymorphism driven by a register shift in a CGAG-rich region found in the promoter of the neurodevelopmental regulatorAUTS2gene

“…All variants fold into secondary structures, which is evident from the presence of imino-proton signals indicating base pairing (Figure 1A ). CD spectra of all variants show negative bands at ∼245 nm and positive bands at ∼275 nm with shoulders at ∼290 nm ( Supplementary Figure S2 ), which are similar to d(GAGC) 5 oligonucleotide ( 47 ). All truncated variants as well as A60 show very similar imino-proton chemical shifts and superimposable CD spectra.…”

Structural properties of DNA oligomers containing (GACX)n and (GAXC)n tandem repeats

“…Low pH stabilization of (GACA) 5 has been reported previously. 28 The sequence (GACC) 7 was significantly more sensitive to pH variations, than any of the other sequences studied, with a stable structure formed at pH 5 (T m 658C). Such structures are often characterized by non-W-C base pairings.…”