ArticleScience advances2022
DNA replication initiation shapes the mutational landscape and expression of the human genome.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Genome-wide mapping of replication stress response factors reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in Leishmania.Nucleic acids research · 2026Article
- Elevated rates and biased spectra of mutations in anaerobically cultured lactic acid bacteria.mBio · 2025Article
- Transcription start sites experience a high influx of heritable variants fueled by early development.Nature communications · 2025Article
- ATR, a DNA damage kinase, modulates DNA replication timing in Leishmania major.PLoS genetics · 2025Article
- Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events.Cell reports · 2025Article
- Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.Nucleic acids research · 2025Review
- 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
- Human-Specific Organization of Proliferation and Stemness in Squamous Epithelia: A Comparative Study to Elucidate Differences in Stem Cell Organization.International journal of molecular sciences · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- DNA replication initiation drives focal mutagenesis and rearrangements in human cancers.Nature communications · 2024Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The interplay between active biological processes and DNA repair is central to mutagenesis. Here, we show that the ubiquitous process of replication initiation is mutagenic, leaving a specific mutational footprint at thousands of early and efficient replication origins. The observed mutational pattern is consistent with two distinct mechanisms, reflecting the two-step process of origin activation, triggering the formation of DNA breaks at the center of origins and local error-prone DNA synthesis in their immediate vicinity. We demonstrate that these replication initiation-dependent mutational processes exert an influence on phenotypic diversity in humans that is disproportionate to the origins' genomic size: By increasing mutational loads at gene promoters and splice junctions, the presence of an origin significantly influences both gene expression and mRNA isoform usage. Last, we show that mutagenesis at origins not only drives the evolution of origin sequences but also contributes to sculpting regulatory domains of the human genome.
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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.