Telomeres are unique nucleoprotein complexes that occur at the termini of eukaryotic chromosomes and are essential for the maintenance of genome integrity and prevention of chromosome degradation and fusion (1). Telomeric DNA is double stranded, consisting of multiple repetitive guanine-rich units (TTAGGG in humans), terminated by ∼300 nucleotide (nt) single-stranded overhang at the 3′-end (1). In vitro, short guanine-rich oligonucleotide sequences can fold into non-canonical DNA secondary structures, called G-quadruplexes (G4s) (2). Over the last decade a large number of proteins and enzymes participating in the regulation of G4 formation (and disruption) have been identified both in vitro and in vivo (3,4). More recently, several groups reported evidences of G4 formation in the genome of eukaryotic cells (5,6). The formation of G4s from exogenous G4 forming DNA sequences was also observed in live Xenopus laevis oocytes (7,8). In addition, a novel high-throughput sequencing technology allowed identifying a vast number of G4 structures and mapping their distribution throughout a human genome (9). Taken together, these observations strongly support the occurrence and functional relevance of G4s in vivo. G4s have been proposed to play a regulatory role in a number of cellular processes such as telomere maintenance, DNA replication, recombination and gene expression (4). They have been found to be involved in several oncological (10) and neurological (11) diseases and are potential targets for pharmacological intervention, utilizing specific G4-binding ligands (10,11). G4 structures are also used in a number of applications for DNA nanotechnology (12).