ArticleNature communications2022
Global landscape of replicative DNA polymerase usage in the human genome.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance.The EMBO journal · 2026Article
- Article
- Article
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- NELF prevents transcriptional readthrough into DNA replication zones in cancer cells.EMBO reports · 2026Article
- Multiplexed TrAEL-seq captures DNA replication dynamics in mammalian cells.Nucleic acids research · 2026Article
- Redox-driven ADAR1 activation promotes Okazaki fragment maturation and DNA replication integrity.Nature structural & molecular biology · 2026Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Sex differences in transcription-associated mutagenesis in the human germline.bioRxiv : the preprint server for biology · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- The Japan-UK Synthetic Biology Conference, Spring 2025: Strengthening Global Links to Engineer Biology.ACS synthetic biology · 2025Article
- Most human DNA replication initiation is dispersed throughout the genome with only a minority within previously identified initiation zones.Genome biology · 2025Article
- Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method.Journal of visualized experiments : JoVE · 2025Article
- Polymerase-usage sequencing identifies initiation zones with less bias across S phase in mouse embryonic stem cells.Journal of biochemistry · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- A tale of two strands: Decoding chromatin replication through strand-specific sequencing.Molecular cell · 2025Review
- Strategic targeting of Cas9 nickase induces large segmental duplications.Cell genomics · 2024Article
- Adaptive use of error-prone DNA polymerases provides flexibility in genome replication during tumorigenesis.Cancer science · 2024Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The division of labour among DNA polymerase underlies the accuracy and efficiency of replication. However, the roles of replicative polymerases have not been directly established in human cells. We developed polymerase usage sequencing (Pu-seq) in HCT116 cells and mapped Polε and Polα usage genome wide. The polymerase usage profiles show Polε synthesises the leading strand and Polα contributes mainly to lagging strand synthesis. Combining the Polε and Polα profiles, we accurately predict the genome-wide pattern of fork directionality plus zones of replication initiation and termination. We confirm that transcriptional activity contributes to the pattern of initiation and termination and, by separately analysing the effect of transcription on co-directional and converging forks, demonstrate that coupled DNA synthesis of leading and lagging strands is compromised by transcription in both co-directional and convergent forks. Polymerase uncoupling is particularly evident in the vicinity of large genes, including the two most unstable common fragile sites, FRA3B and FRA3D, thus linking transcription-induced polymerase uncoupling to chromosomal instability. Together, our result demonstrated that Pu-seq in human cells provides a powerful and straightforward methodology to explore DNA polymerase usage and replication fork dynamics.
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Registered trials
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.