ArticleGenes & development2008
Overreplication of short DNA regions during S phase in human cells.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication.Nature communications · 2026Article
- RAD51 restricts DNA over-replication from re-activated origins.The EMBO journal · 2024Article
- 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.Nucleic acids research · 2022Article
- Review
- Review
- Peaks cloaked in the mist: the landscape of mammalian replication origins.The Journal of cell biology · 2015Review
- R-loops and initiation of DNA replication in human cells: a missing link?Frontiers in genetics · 2015Article
- The hunt for origins of DNA replication in multicellular eukaryotes.F1000prime reports · 2015Review
- Dnase2a deficiency uncovers lysosomal clearance of damaged nuclear DNA via autophagy.Cell reports · 2014Article
- High-resolution analysis of DNA synthesis start sites and nucleosome architecture at efficient mammalian replication origins.The EMBO journal · 2013Article
- Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features.Genome research · 2011Article
- Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks.Nature structural & molecular biology · 2011Article
- CpG island chromatin: a platform for gene regulation.Epigenetics · 2011Article
- Article
- Eukaryotic DNA replication origins: many choices for appropriate answers.Nature reviews. Molecular cell biology · 2010Review
- A winding road to origin discovery.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2010Article
- Fragile genomic sites are associated with origins of replication.Genome biology and evolution · 2009Article
- Long-range bidirectional strand asymmetries originate at CpG islands in the human genome.Genome biology and evolution · 2009Article
- Transcription initiation activity sets replication origin efficiency in mammalian cells.PLoS genetics · 2009Article
- Analysis of re-replication from deregulated origin licensing by DNA fiber spreading.Nucleic acids research · 2009Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA replication origins (ORI) are regulatory regions from which the genome is replicated once every cell cycle. A widely used method for their identification in mammalian chromosomes relies on quantitative PCR of DNA nascent strands across candidate regions. We developed a new high-resolution PCR strategy to localize ORIs directly on total unfractionated human DNA. The increase in sensitivity provided by this approach has revealed that a short region of approximately 200-base-pair overlapping well-characterized replication origins undergoes several rounds of replication, coinciding with their specific time of activation during S phase. This process generates a population of discrete dsDNA fragments detectable as free molecules in preparations of total DNA in normally proliferating cells. Overreplicated regions have precise boundaries at the edge of the nucleosome-free gap that encompasses the transcription initiation sites of CpG island promoters. By itself, active transcription does not induce overreplication but does stimulate it at ORIs associated with promoters. The coincidence in time and space between the overproduction of short DNA fragments and ORI activity predicts the precise localization of thousands of ORIs in the human genome and uncovers a previously unnoticed step in the initiation of DNA replication.
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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.