ArticleNucleic acids research2022
Determination of human DNA replication origin position and efficiency reveals principles of initiation zone organisation.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Spatial organization and dynamics of genome replication: from forks to foci.Nucleic acids research · 2026Review
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- Replication Rate-Information Storage Trade-Off Shapes Genome Architecture Across Domains.Journal of molecular evolution · 2026Article
- Improved short nascent strand sequencing (iSNS-seq) enhances DNA replication origin detection and reduces non-origin biases.bioRxiv : the preprint server for biology · 2026Article
- OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells.Nature communications · 2026Article
- Comparative analysis of single-stranded and non-canonical DNA formation in human and other ape cells with telomere-to-telomere genomes.bioRxiv : the preprint server for biology · 2025Article
- Mammalian H4K16ac regulates the spatiotemporal order of genome replication rather than gene expression.Nucleic acids research · 2025Article
- Master transcription-factor binding sites constitute the core of early replication control elements.The EMBO journal · 2025Article
- ecDNA replication is disorganized and vulnerable to replication stress.Nucleic acids research · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Cell cycle-dependent TICRR/TRESLIN and MTBP chromatin binding mechanisms and patterns.Genome biology · 2025Article
- Loss of G1-phase CDK-inhibition biases instability between genomic regions by unevenly reducing activity among replication origins.iScience · 2025Article
- Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.Nucleic acids research · 2025Article
- Most human DNA replication initiation is dispersed throughout the genome with only a minority within previously identified initiation zones.Genome biology · 2025Article
- Human DNA replication initiation sites are specified epigenetically by oxidation of 5-methyl-deoxycytidine.Nucleic acids research · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- The epigenetic landscape shapes smoking-induced mutagenesis by modulating DNA damage susceptibility and repair efficiency.Nucleic acids research · 2025Article
- R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania.Nature communications · 2025Article
- A tale of two strands: Decoding chromatin replication through strand-specific sequencing.Molecular cell · 2025Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Replication of the human genome initiates within broad zones of ∼150 kb. The extent to which firing of individual DNA replication origins within initiation zones is spatially stochastic or localised at defined sites remains a matter of debate. A thorough characterisation of the dynamic activation of origins within initiation zones is hampered by the lack of a high-resolution map of both their position and efficiency. To address this shortcoming, we describe a modification of initiation site sequencing (ini-seq), based on density substitution. Newly replicated DNA is rendered 'heavy-light' (HL) by incorporation of BrdUTP while unreplicated DNA remains 'light-light' (LL). Replicated HL-DNA is separated from unreplicated LL-DNA by equilibrium density gradient centrifugation, then both fractions are subjected to massive parallel sequencing. This allows precise mapping of 23,905 replication origins simultaneously with an assignment of a replication initiation efficiency score to each. We show that origin firing within early initiation zones is not randomly distributed. Rather, origins are arranged hierarchically with a set of very highly efficient origins marking zone boundaries. We propose that these origins explain much of the early firing activity arising within initiation zones, helping to unify the concept of replication initiation zones with the identification of discrete replication origin sites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.