Contributions of the specialised DNA polymerases to replication of structured DNA

Wickramasinghe, Caroline M.; Arzouk, Hayat; Frey, Alexander D.; Maiter, Ahmed; Sale, Julian E.

doi:10.1016/j.dnarep.2015.01.004

Cited by 39 publications

(33 citation statements)

References 81 publications

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“…Four broadly defined components underlie HR-associated mutagenesis: polymerase choice, processivity, donor choice, and template integrity (Figure 3). In addition, HR involving DNA sequences with the potential to form secondary structures may lead to genetic and epigenetic instability (154). Together, these components mediate mutagenesis and have their own respective propensities for generating small-scale mutations and/or gross chromosomal rearrangements.…”

Section: Recombination-associated Mutagenesismentioning

confidence: 99%

Eukaryotic DNA Polymerases in Homologous Recombination

et al. 2016

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Homologous recombination (HR) is a central process to ensure genomic stability in somatic cells and during meiosis. HR-associated DNA synthesis determines in large part the fidelity of the process. A number of recent studies have demonstrated that DNA synthesis during HR is conservative, less processive, and more mutagenic than replicative DNA synthesis. In this review, we describe mechanistic features of DNA synthesis during different types of HR-mediated DNA repair, including synthesis-dependent strand annealing, break-induced replication, and meiotic recombination. We highlight recent findings from diverse eukaryotic organisms, including humans, that suggest both replicative and translesion DNA polymerases are involved in HR-associated DNA synthesis. Our focus is to integrate the emerging literature about DNA polymerase involvement during HR with the unique aspects of these repair mechanisms, including mutagenesis and template switching.

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Section: Recombination-associated Mutagenesismentioning

confidence: 99%

Eukaryotic DNA Polymerases in Homologous Recombination

et al. 2016

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“…The other TLS polymerases play a minor role in the DT40 system and only small epigenetic alterations at the β-globin and at the Bu1a loci are observed in single pol η and pol κ knockouts. Furthermore, even the triple pol η/ pol κ/ rev3 mutant does not show changes comparable to the one observed in rev1 (Wickramasinghe et al, 2015). Thus, the role of Rev1 appears to be independent from the other TLS polymerases and its C-terminus might interact with additional factors involved in DNA replication such helicases and possibly even replicative polymerases.…”

Section: G4 Replication and Epigenetic Instabilitymentioning

confidence: 75%

Replication of Structured DNA and its implication in epigenetic stability

2015

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DNA replication is an extremely risky process that cells have to endure in order to correctly duplicate and segregate their genome. This task is particularly sensitive to DNA damage and multiple mechanisms have evolved to protect DNA replication as a block to the replication fork could lead to genomic instability and possibly cell death. The DNA in the genome folds, for the most part, into the canonical B-form but in some instances can form complex secondary structures such as G-quadruplexes (G4). These G rich regions are thermodynamically stable and can constitute an obstacle to DNA and RNA metabolism. The human genome contains more than 350,000 sequences potentially capable to form G-quadruplexes and these structures are involved in a variety of cellular processes such as initiation of DNA replication, telomere maintenance and control of gene expression. Only recently, we started to understand how G4 DNA poses a problem to DNA replication and how its successful bypass requires the coordinated activity of ssDNA binding proteins, helicases and specialized DNA polymerases. Their role in the resolution and replication of structured DNA crucially prevents both genetic and epigenetic instability across the genome.

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“…one or more offset hairpins on complementary DNA strands) [14–16], DNA triplexes (H-DNA) [17] and guanine quadruplexes [18,19]. Following in vitro replication, mono-nucleotide and dinucleotide repeats show >10-fold elevated rates of frame shift mutations over control template sequences [20–22].…”

Section: Microsatellite Dnas Adopt Non-watson-crick Secondary Strumentioning

confidence: 99%

Replication stalling and DNA microsatellite instability

Gadgil

Barthelemy

Lewis

et al. 2017

Biophysical Chemistry

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Microsatellites are short, tandemly repeated DNA motifs of 1–6 nucleotides, also termed simple sequence repeats (SRSs) or short tandem repeats (STRs). Collectively, these repeats comprise approximately 3% of the human genome Subramanian et al. (2003), Lander and Lander (2001) [1,2], and represent a large reservoir of loci highly prone to mutations Sun et al. (2012), Ellegren (2004) [3,4] that contribute to human evolution and disease. Microsatellites are known to stall and reverse replication forks in model systems Pelletier et al. (2003), Samadashwily et al. (1997), Kerrest et al. (2009) [5–7], and are hotspots of chromosomal double strand breaks (DSBs). We briefly review the relationship of these repeated sequences to replication stalling and genome instability, and present recent data on the impact of replication stress on DNA fragility at microsatellites in vivo.

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Contributions of the specialised DNA polymerases to replication of structured DNA

Cited by 39 publications

References 81 publications

Eukaryotic DNA Polymerases in Homologous Recombination

Eukaryotic DNA Polymerases in Homologous Recombination

Replication of Structured DNA and its implication in epigenetic stability

Replication stalling and DNA microsatellite instability

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