RESEARCH ARTICLE G-Quadruplexes Involving Both Strands of Genomic DNA Are Highly Abundant and Colocalize with Functional Sites in the Human

The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replica-tion, transcription and telomere stability. To date, only G4s with all guanines originating from the same strand of DNA have been considered in the context of the human nuclear genome. Here, I discuss interstrand topological configurations of G-quadruplex DNA, con-sisting of guanines from both strands of genomic DNA; an algorithm is presented for predict-ing such structures. I have identified over 550,000 non-overlapping interstrand G-quadruplex forming sequences in the human genome—significantly more than intrastrand configurations. Functional analysis of interstrand G-quadruplex sites shows strong associa-tion with transcription initiation, the results are consistent with the XPB and XPD transcrip-tional helicases binding only to G-quadruplex DNA with interstrand topology. Interstrand quadruplexes are also enriched in origin of replication sites. Several topology classes of interstrand quadruplex-forming sequences are possible, and different topologies are enriched in different types of structural elements. The list of interstrand quadruplex forming sequences, and the computer program used for their prediction are available at the web addres