Secondary structures in d(CGG) and d(CCG) repeat tracts

Abstract

Several studies have been made to elucidate the nature of secondary structures in the single strands of d(CGG).d(CCG) repeat tracts but with conflicting conclusions. Here, we review this work and attempt to come towards consensus. Some investigators find that the G-rich strand forms hairpins. Of these, some conclude that pairing is in the alignment d(GGC).d(GGC) with two Watson-Crick bonds and one G.G bond per duplex repeat, others conclude that the alignment is d(GCG).d(GCG) with two G.G bonds and one C.C bond per duplex repeat. Others find quadruplex formation and conclude that this is in the latter alignment with two G4-quartets per quadruplex repeat and C.C bonds. We investigate why these different results were obtained and conclude that quadruplexes are likely to form under physiological conditions. We argue that they are probably bonded in the alignment d(GGC).d(GGC) with one G4-quartet and two C.G.C.G. quartets per quadruplex repeat. The C-rich strand does not appear to form quadruplexes under physiological conditions but forms hairpins. Apparently, short hairpins adopt the alignment d(CCG).d(CCG) with mismatched cytosine residues stacked into the helix but with 15 or more repeat units, the dominant form is a distorted hairpin aligned as d(GCC).d(GCC) with unpaired cytosine residues possibly turned outwards and stacked in the minor groove.