ArticleGenome research2015
Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins.
Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- Improved short nascent strand sequencing (iSNS-seq) enhances DNA replication origin detection and reduces non-origin biases.bioRxiv : the preprint server for biology · 2026Article
- Stranded short nascent strand sequencing reveals the topology of DNA replication origins ineLife · 2026Article
- Nanopore-based sequencing of active DNA replication reveals key principles of metazoan replication dynamics.Science advances · 2026Article
- ssG4-seq for global profiling of strand-specific G-quadruplex structures in mammalian genomes.Nature communications · 2025Article
- Article
- Nanopore-based sequencing of active DNA replication reveals key principles of metazoan replication fork progression, origin and termination sites.bioRxiv : the preprint server for biology · 2025Article
- Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events.Cell reports · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- Article
- Identification of a viral gene essential for the genome replication of a domesticated endogenous virus in ichneumonid parasitoid wasps.PLoS pathogens · 2024Article
- Review
- G4access identifies G-quadruplexes and their associations with open chromatin and imprinting control regions.Nature genetics · 2023Article
- Article
- 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.Nucleic acids research · 2022Article
- Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022Article
- Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy.Nucleic acids research · 2022Article
- Article
- Genome-wide mapping of human DNA replication by optical replication mapping supports a stochastic model of eukaryotic replication.Molecular cell · 2021Article
- Folding and persistence times of intramolecular G-quadruplexes transiently embedded in a DNA duplex.Nucleic acids research · 2021Article
- A predictable conserved DNA base composition signature defines human core DNA replication origins.Nature communications · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na(+) instead of K(+) in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq.
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