ArticleNature2015
Lagging-strand replication shapes the mutational landscape of the genome.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 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.
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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
162 citing papers in PubMed, 252 citations in OpenAlex.
- Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance.The EMBO journal · 2026Article
- Reconstituting human and SV40 replisomes with Okazaki fragment maturation reveals synchronized leading- and lagging-strand synthesis.Nature communications · 2026Article
- Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026Review
- CST complex promotes second-strand synthesis in break-induced replication.Nature structural & molecular biology · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- DNA Mechanical Strain Steers Transcription Factor Recognition.Research square · 2026Article
- CTCF/cohesin-binding sites are susceptible to replication-associated DNA damage and genomic instability in cancer cells.iScience · 2026Article
- ADAR1 is an editor of DNA replication forks.Nature structural & molecular biology · 2026Article
- Genome-wide ribonucleotide detection in Archaea.Nucleic acids research · 2025Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- The eukaryotic replisome intrinsically generates asymmetric daughter chromatin fibers.bioRxiv : the preprint server for biology · 2025Article
- DNA polymerase α-primase can function as a translesion DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The human primosome requires replication protein A when copying DNA with inverted repeats.Nucleic acids research · 2025Article
- Evidence that transient replication errors initiate nuclear genome mutations.Nucleic acids research · 2025Article
- Systematic DNA nicking reveals the structural logic of protein recognition.bioRxiv : the preprint server for biology · 2025Article
- Article
- 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
- 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
- Evidence that DNA polymerase δ proofreads errors made by DNA polymerase α across the Saccharomyces cerevisiae nuclear genome.DNA repair · 2024Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The origin of mutations is central to understanding evolution and of key relevance to health. Variation occurs non-randomly across the genome, and mechanisms for this remain to be defined. Here we report that the 5' ends of Okazaki fragments have significantly increased levels of nucleotide substitution, indicating a replicative origin for such mutations. Using a novel method, emRiboSeq, we map the genome-wide contribution of polymerases, and show that despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-α (Pol-α) is retained in vivo, comprising approximately 1.5% of the mature genome. We propose that DNA-binding proteins that rapidly re-associate post-replication act as partial barriers to Pol-δ-mediated displacement of Pol-α-synthesized DNA, resulting in incorporation of such Pol-α tracts and increased mutation rates at specific sites. We observe a mutational cost to chromatin and regulatory protein binding, resulting in mutation hotspots at regulatory elements, with signatures of this process detectable in both yeast and humans.
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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.