ArticleeLife2024
Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Polycomb-mediated 3D-genome organization controls replication timing.Science advances · 2026Article
- Stranded short nascent strand sequencing reveals the topology of DNA replication origins ineLife · 2026Article
- Nanopore-based sequencing of active DNA replication reveals key principles of metazoan replication dynamics.Science advances · 2026Article
- The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.FEBS letters · 2026Article
- OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells.Nature communications · 2026Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- Nanopore-based sequencing of active DNA replication reveals key principles of metazoan replication fork progression, origin and termination sites.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms for licensing origins of DNA replication in eukaryotic cells.Nature structural & molecular biology · 2025Review
- Regulation of epigenetics and chromosome structure by human ORC2.Cell reports · 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
- LncRNAs Ride the Storm of Epigenetic Marks.Genes · 2025Review
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- 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
- Archaeal DNA replication initiation: bridging LUCA's legacy and modern mechanisms.Frontiers in microbiology · 2025Article
- Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Review
- The Origin Recognition Complex: From Origin Selection to Replication Licensing in Yeast and Humans.Biology · 2023Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the origin recognition complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and five ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features. Out of ~7.5 million union origins identified by all datasets, only 0.27% (20,250 shared origins) were reproducibly obtained in at least 20 independent SNS-seq datasets and contained in initiation zones identified by each of three other techniques, suggesting extensive variability in origin usage and identification. Also, 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF-binding sites, G-quadruplex sites, and activating histone marks, these overlaps are comparable or less than that of known transcription start sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ~13,000 reproducible ORC-binding sites in human cancer cells, and only 4.5% were within 1 kb of the ~11,000 union MCM2-7-binding sites in contrast to the nearly 100% overlap in the two comparisons in the yeast,
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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.