Prevalence of quadruplexes in the human genome

Abstract

Guanine-rich DNA sequences of a particular form have the ability to fold into four-stranded structures called G-quadruplexes. In this paper, we present a working rule to predict which primary sequences can form this structure, and describe a search algorithm to identify such sequences in genomic DNA. We count the number of quadruplexes found in the human genome and compare that with the figure predicted by modelling DNA as a Bernoulli stream or as a Markov chain, using windows of various sizes. We demonstrate that the distribution of loop lengths is significantly different from what would be expected in a random case, providing an indication of the number of potentially relevant quadruplex-forming sequences. In particular, we show that there is a significant repression of quadruplexes in the coding strand of exonic regions, which suggests that quadruplex-forming patterns are disfavoured in sequences that will form RNA.

G-quadruplexes: selective DNA targeting for cancer therapeutics?

“…As a result, nonvalidated G-quadruplex targets have been used to identify potent binders. This reverse-genetics approach seems to have revealed a number of targets, including telomeres [8]. Whether these molecules are able to bind and target one specific or clusters of G-quadruplex structures is still an open question.…”

Nucleophosmin mutations in acute myeloid leukemia: A tale of protein unfolding and mislocalization

“…46,47 They can be formed both by DNA and RNA, and they are abundant at telomeric DNA, gene promoters, and mRNA 5 0 -UTRs. 48,49 The importance of these structures in regulating several cellular processes at the translational and posttranslational levels is emerging clearly and a number of proteins have been shown to interact with and to stabilize or destabilize the G-quadruplex fold. 50 A well-characterized G-quadruplex sequence is present at the nuclease hypersensitive element III (NHE III ) of the c-MYC promoter, and regulates up to 90% of c-MYC gene transcription.…”

Probing Human Telomeric DNA and RNA Topology and Ligand Binding in a Cellular Model by Using Responsive Fluorescent Nucleoside Probes

“…The position and conservation of putative GQ‐forming motifs, particularly among mammalian species, as evident from bioinformatics and sequencing studies, suggest that GQ could be an important class of structural element for gene regulation 2. In the human genome, GQ‐forming sequences are mostly found in the telomeric region (e.g., telomeric DNA and RNA repeats) and in several DNA promoters (e.g., C‐myc, C‐kit) and untranslated regions of mRNA (e.g., NRAS, BCL‐2) 3, 4.…”