Abstract
: G4 DNA is a non-canonical DNA structure consisting of a stacked array of G-quartets held together by base pairing between guanine bases. The formation of G4 DNA requires a cluster of guanine-runs within a strand of DNA. Even though the chemistry of this remarkable DNA structure has been under investigation for decades, evidence supporting the biological relevance of G4 DNA has only begun to emerge and point to very important and conserved biological functions. This review will specifically focus on the interplay between transcription and G4 DNA and discuss two alternative but interconnected perspectives. The first part of the review will describe the evidence substantiating the intriguing idea that a shift in DNA structural conformation could be another layer of non-genetic or epigenetic regulator of gene expression and thereby an important determinant of cell fate. The second part will describe the recent genetic studies showing that those genomic loci containing G4 DNA-forming guanine-rich sequences are potential hotspots of genome instability and that the level and orientation of transcription is critical in the materialization of genome instability associated with these sequences.
Highlights
Free guanine bases in solution readily interact with each other via Hoogsten bonds to form a fourmembered ring-like structure referred to as a G-quartet [1]
Among the various non-B DNA structures that are recently being investigated as the significant instigators of genome instability, G4 DNA is uniquely implicated as a key element of the deliberate, regulated recombination programs such as the vertebrate Ig Class Switch Recombination (CSR) and bacterial antigenic variation (Av)
The findings from the yeast genetic assays utilizing the G4 forming sequences embedded in the recombination reporter constructs, together with the molecular details uncovered regarding the mechanisms CSR and Av recombination processes, revealed the critical role of transcription in transforming G4 motifs into genome instability hotspot
Summary
Free guanine bases in solution readily interact with each other via Hoogsten bonds to form a fourmembered ring-like structure referred to as a G-quartet [1]. G-quaduplex or G4 DNA, comprising multiple Gquartets stabilized by stacking readily form from single-stranded oligonucleotides in solution. The presence of various cations, such as K+, Na+, Ca2+, and Sr2+, facilitates the G4 DNA formation with K+ having the most stabilizing effect. Nucleosides between guanineruns are incorporated into the structure as loops between G-quartets, and the size of the loops can determine the relative stability of various G4 DNA configurations. Sequences with potential to form G4 DNA or “G4 motifs” were first noted at the telomeres, ribosomal DNA arrays, Immunoglobulin (Ig) heavy chain
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