ArticleGenes & development2005
Recruitment of ORC or CDC6 to DNA is sufficient to create an artificial origin of replication in mammalian cells.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 76 citations in OpenAlex.
- Article
- A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin.The EMBO journal · 2023Article
- Deletion of Orc4 during oogenesis severely reduces polar body extrusion and blocks zygotic DNA replication†.Biology of reproduction · 2022Article
- Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry.Nucleic acids research · 2021Article
- Regulation of DNA Replication Licensing and Re-Replication by Cdt1.International journal of molecular sciences · 2021Review
- The role of ORC4 in enucleation of Murine Erythroleukemia (MEL) cells is similar to that in oocyte polar body extrusion.Systems biology in reproductive medicine · 2020Article
- INO80C Remodeler Maintains Genomic Stability by Preventing Promiscuous Transcription at Replication Origins.Cell reports · 2020Article
- Regulation of the initiation of DNA replication in human cells.DNA repair · 2018Review
- Higher Order Oligomerization of the Licensing ORC4 Protein Is Required for Polar Body Extrusion in Murine Meiosis.Journal of cellular biochemistry · 2017Article
- From structure to mechanism-understanding initiation of DNA replication.Genes & development · 2017Review
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
- Rethinking origin licensing.eLife · 2017Article
- The LMO2 oncogene regulates DNA replication in hematopoietic cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- ORC proteins in the mammalian zygote.Cell and tissue research · 2016Review
- Genome Duplication: The Heartbeat of Developing Organisms.Current topics in developmental biology · 2016Review
- Post-licensing Specification of Eukaryotic Replication Origins by Facilitated Mcm2-7 Sliding along DNA.Molecular cell · 2015Article
- Initiation of replication in Xenopus egg extracts at a spatially defined origin.Cell cycle (Georgetown, Tex.) · 2015Article
- Peaks cloaked in the mist: the landscape of mammalian replication origins.The Journal of cell biology · 2015Review
- RecQ4 promotes the conversion of the pre-initiation complex at a site-specific origin for DNA unwinding in Xenopus egg extracts.Cell cycle (Georgetown, Tex.) · 2015Article
- Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication.The EMBO journal · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Origins of replication are expected to recruit initiation proteins like origin recognition complex (ORC) and Cdc6 in eukaryotes and provide a platform for unwinding DNA. Here we test whether localization of initiation proteins onto DNA is sufficient for origin function. Different components of the ORC complex and Cdc6 stimulated prereplicative complex (pre-RC) formation and replication initiation when fused to the GAL4 DNA-binding domain and recruited to plasmid DNA containing a tandem array of GAL4-binding sites. Replication occurred once per cell cycle and was inhibited by Geminin, indicating that the plasmid was properly licensed during the cell cycle. The GAL4 fusion protein recruits other polypeptides of the ORC-Cdc6 complex, and nascent strand abundance was highest near the GAL4-binding sites. Therefore, the artificial origin recapitulates many of the regulatory features of physiological origins and is valuable for studies on replication initiation in mammalian cells. We demonstrated the utility of this system by showing the functional importance of the ATPase domains of human Cdc6 and Orc1 and the dispensability of the N-terminal segments of Orc1 and Orc2 in this assay. Artificial recruitment of a eukaryotic cellular replication initiation factor to a DNA sequence can create a functional origin of replication, providing a robust genetic assay for these factors and a novel approach to generating episomal vectors for gene therapy.
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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.