Abstract
A cursory look at any textbook image of DNA replication might suggest that the complex machine that is the replisome runs smoothly along the chromosomal DNA. However, many DNA sequences can adopt non-B form secondary structures and these have the potential to impede progression of the replisome. A picture is emerging in which the maintenance of processive DNA replication requires the action of a significant number of additional proteins beyond the core replisome to resolve secondary structures in the DNA template. By ensuring that DNA synthesis remains closely coupled to DNA unwinding by the replicative helicase, these factors prevent impediments to the replisome from causing genetic and epigenetic instability. This review considers the circumstances in which DNA forms secondary structures, the potential responses of the eukaryotic replisome to these impediments in the light of recent advances in our understanding of its structure and operation and the mechanisms cells deploy to remove secondary structure from the DNA. To illustrate the principles involved, we focus on one of the best understood DNA secondary structures, G quadruplexes (G4s), and on the helicases that promote their resolution.
Highlights
A cursory look at any textbook image of DNA replication might suggest that the complex machine that is the replisome runs smoothly along the chromosomal DNA
Using our approach of monitoring epigenetic instability in DT40 cells, we have shown that G4s can interrupt leading strand DNA synthesis when cells lack a number of factors e.g. the specialised polymerase REV1, specialised helicases FANCJ, BLM
In vivo, other factors need to be considered, not least of which is the state of the adjacent DNA, the torsional and longitudinal forces locally acting on the DNA and the presence of DNA-binding proteins and nucleosomes
Summary
The majority of DNA within a cell exists in the canonical double-stranded B-form, transactions on DNA such as transcription and replication require the duplex to be unwound. This diversity is largely upon the height of examples the G quartet stackare and length of the 1D. G4 focus formation has been studied in vitro for that many it is only recently that converging a topic debate They been linked to transcriptional [17], telomere maintenance [18,19]. Perfectly possible that many the sequences that are topic of debate They have beenIndeed, linked it toistranscriptional regulation [17],oftelomere maintenance capableand of forming. G4s are associated with an increased risk of potentially deleterious genetic and epigenetic events linked to replication [24,25,26,27]
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