ArticleProceedings of the National Academy of Sciences of the United States of America2016
Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 200 citations in OpenAlex.
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- Nanopore-based sequencing of active DNA replication reveals key principles of metazoan replication dynamics.Science advances · 2026Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- Nuclear DAB2IP regulates DNA replication initiation through activating PLK1-mediated HBO1 phosphorylation.Nucleic acids research · 2025Article
- HIRA defines early replication initiation zones independently of their genome compartment.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
- DNA replication initiation timing is important for maintaining genome integrity.Journal of bacteriology · 2025Article
- BAHCC1 binds H4K20me1 to facilitate the MCM complex loading and DNA replication.Nature communications · 2025Article
- Regulation of epigenetics and chromosome structure by human ORC2.Cell reports · 2025Article
- DNA bending mediated by ORC is essential for replication licensing in budding yeast.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- Non-canonical functions of enhancers: regulation of RNA polymerase III transcription, DNA replication, and V(D)J recombination.Trends in genetics : TIG · 2024Article
- Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression.Genome biology · 2024Article
- The dimeric deubiquitinase USP28 integrates 53BP1 and MYC functions to limit DNA damage.Nucleic acids research · 2024Article
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- RAD51 restricts DNA over-replication from re-activated origins.The EMBO journal · 2024Article
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- The genetic landscape of origins of replication in P. falciparum.Nucleic acids research · 2024Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not bound or recruited to specific DNA sequences. Instead, ORC binds nonspecifically to open (DNase I-hypersensitive) regions containing active chromatin marks such as H3 acetylation and H3K4 methylation. ORC sites in early and late replicating regions have similar properties, but there are far more ORC sites in early replicating regions. This suggests that replication timing is due primarily to ORC density and stochastic firing of origins. Computational simulation of stochastic firing from identified ORC sites is in accord with replication timing data. Large genomic regions with a paucity of ORC sites are strongly associated with common fragile sites and recurrent deletions in cancers. We suggest that replication origins, replication timing, and replication-dependent chromosome breaks are determined primarily by the genomic distribution of activator proteins at enhancers and promoters. These activators recruit nucleosome-modifying complexes to create the appropriate chromatin structure that allows ORC binding and subsequent origin firing.
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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.