Abstract
G-quadruplexes are four-stranded guanine-rich structures that have been demonstrated to occur across the genome in humans and other organisms. They provide regulatory functions during transcription, translation and immunoglobulin gene rearrangement, but there is also a large amount of evidence that they can present a potent barrier to the DNA replication machinery. This mini-review will summarize recent advances in understanding the many strategies nature has evolved to overcome G-quadruplex-mediated replication blockage, including removal of the structure by helicases or nucleases, or circumventing the deleterious effects on the genome through homologous recombination, alternative end-joining or synthesis re-priming. Paradoxically, G-quadruplexes have also recently been demonstrated to provide a positive role in stimulating the initiation of DNA replication. These recent studies have not only illuminated the many roles and consequences of G-quadruplexes, but have also provided fundamental insights into the general mechanisms of DNA replication and its links with genetic and epigenetic stability.
Highlights
Guanine-rich DNA has a well-characterized ability to form into four-stranded structures known asG-quadruplexes (G4s), stabilized by hydrogen bonding between a planar association of four guanines [1].Once thought to be an in vitro curiosity, G-quadruplexes are known to form throughout genomes in vivo, where they perform positive regulatory roles in addition to potentially having deleterious effects on genome stability
G-quadruplexes have many beneficial functions in the genome: they protect telomeres, form binding sites for transcription factors, regulate translation and promote immunoglobulin gene recombination. These roles of G-quadruplexes have been the subject of several reviews [13,14,15]; here we will instead focus on the consequences of G-quadruplex formation for DNA replication
Direct evidence for the impact of G-quadruplexes on replication in vivo has come from experiments using single-molecule analysis of replicating DNA, in which DNA molecules are stretched on microscope slides and the patterns of nucleotide incorporation are detected using fluorescence in situ hybridization (FISH) [40]
Summary
Guanine-rich DNA has a well-characterized ability to form into four-stranded structures known as. G-quadruplexes have many beneficial functions in the genome: they protect telomeres, form binding sites for transcription factors, regulate translation and promote immunoglobulin gene recombination These roles of G-quadruplexes have been the subject of several reviews [13,14,15]; here we will instead focus on the consequences of G-quadruplex formation for DNA replication. Ensuing deletions, recombination and genetic instability can be lethal to the cell This mini-review will describe these exciting recent advances in understanding hand, recent data point to a positive role for. This mini-review willofdescribe these exciting recent advances understanding the interplay between biological effects these fascinating structures, but havein provided fundamental insights into These studies have revealed the biological effects of the mechanisms by which DNA replication is coupled to epigenetic gene regulation and genome these fascinating structures, but have provided fundamental insights into the mechanisms by stability. Homologous recombination mediated by RAD51, BRCA1, and BRCA2 can lead to genomic
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