Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops

Abstract

THE telomeric ends of eukaryotic chromosomes are composed of simple repeating sequences in which one DNA strand contains short tracts of guanine residues alternating with short tracts of A/T-rich sequences^1,2. The guanine-rich strand is always oriented in a 5′–3′ direction towards the end of the chromosome and is extended to produce a 3′ overhang of about two repeating units in species where the telomeric terminus is known^3,4. This overhang has been implicated in the formation of several unusual intra- and intermolecular DNA structures^5–9, although none of these structures has been characterized fully. We now report that oligo-nucleotides encoding Tetrahymena telomeres dimerize to form stable complexes in solution. This salt-dependent dimerization is mediated entirely by the 3′-terminal telomeric overhang (TT-GGGGTTGGGG) and produces complexes in which the N7 position of every guanine in the overhangs is chemically inaccessible. We therefore propose that telomeric DNA dimerizes by hydrogen bonding between two intramolecular hairpin loops⁵, to form anti-parallel quadruplexes containing cyclic guanine base tetrads. These novel hairpin dimers may be important in telomere association and recombination and could also provide a general mechanism for pairing two double helices in other recombinational processes.