G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide

Enrico Lavezzo; Michele Berselli; Ilaria Frasson; Rosalba Perrone; Giorgio Palù; Alessandra R. Brazzale; Sara N. Richter; Stefano Toppo

G-quadruplexes (G4s) are nucleic acids secondary structures that may form in singlestranded DNA and RNA G-rich sequences under physiological conditions (Lipps and Rhodes 2009 ). Four Gs bind via Hoogsteen-type base-pairing to yield G-quartets: stacking of at least two G-quartets leads to G4 formation, through π-π interactions between aromatic systems of G-quartets. K + cations in the central cavity relieve repulsion among oxygen atoms and specifically support G4 formation and stability (Sen and Gilbert 1990) . In the human genome, putative DNA G4 forming regions are clustered at definite genomic regions, such as telomeres, oncogene promoters, immunoglobulin switch regions, DNA replication origins and recombination sites (Maizels and Gray 2013) . Actual G4s were shown to be involved in key regulatory roles, including transcriptional regulation of gene promoters and enhancers, translation, chromatin epigenetic regulation, and DNA recombination (Perrone et al. 2013a; Holder and Hartig 2014; Maizels 2015; Rhodes and Lipps 2015; Zhou et al. 2015) .