G4 DNA is a non-canonical DNA structure consisting of a stacked array of Gquartets
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.
Keywords: G4 DNA, transcription, R-loops, Top1, supercoiling, genome stability.
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