Abstract
The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replication, 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, consisting of guanines from both strands of genomic DNA; an algorithm is presented for predicting 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 association with transcription initiation, the results are consistent with the XPB and XPD transcriptional 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 address http://moment.utmb.edu/allquads.
Highlights
The G-quadruplex (G4) is a non-canonical DNA structure consisting of four strands stabilized by Hoogsteen bonds that has received significant attention in the recent years
My approach to finding interstrand quadruplex-forming sequences differs from the approach of Cao et al [13] in that here a separate one-step search is performed for each topology class, while Cao et al first identify DNA intervals with quadruplex-forming potential and characterize the topology of the possible quadruplex
A complete Perl program and the results for the hg19 human genome assembly are available as supplementary data, and from the supporting website http://moment.utmb.edu/allquads
Summary
The G-quadruplex (G4) is a non-canonical DNA structure consisting of four strands stabilized by Hoogsteen bonds that has received significant attention in the recent years. G4s have been implicated in numerous cellular contexts and functions [1,2], including telomeres [3], cis-acting regulatory elements [4], transcription [5], and replication [6,7,8]. Four runs of guanine must be present in the DNA sequence from which a G4 is created [9,10]. While bimolecular or tetramolecular G-quadruplexes have been discussed in the context of short oligomers, or of PLOS ONE | DOI:10.1371/journal.pone.0146174. While bimolecular or tetramolecular G-quadruplexes have been discussed in the context of short oligomers, or of PLOS ONE | DOI:10.1371/journal.pone.0146174 January 4, 2016
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