ArticleMolecular and cellular biology2003
Multiple functional elements comprise a Mammalian chromosomal replicator.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 95 citations in OpenAlex.
- Microsatellite break-induced replication generates highly mutagenized extrachromosomal circular DNAs.NAR cancer · 2024Article
- Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes.Nucleus (Austin, Tex.) · 2023Review
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- Stable G-quadruplex DNA structures promote replication-dependent genome instability.The Journal of biological chemistry · 2022Article
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- The genetic architecture of DNA replication timing in human pluripotent stem cells.Nature communications · 2021Observational
- Replication stress at microsatellites causes DNA double-strand breaks and break-induced replication.The Journal of biological chemistry · 2020Article
- Deficiency of the Fanconi anemia E2 ubiqitin conjugase UBE2T only partially abrogates Alu-mediated recombination in a new model of homology dependent recombination.Nucleic acids research · 2019Article
- Article
- Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability.Nucleic acids research · 2017Article
- Replication stalling and DNA microsatellite instability.Biophysical chemistry · 2017Review
- Order from clutter: selective interactions at mammalian replication origins.Nature reviews. Genetics · 2017Review
- Regulation of Replication Origins.Advances in experimental medicine and biology · 2017Review
- FANCJ is essential to maintain microsatellite structure genome-wide during replication stress.Nucleic acids research · 2016Article
- Replication origins: determinants or consequences of nuclear organization?Current opinion in genetics & development · 2016Review
- Peaks cloaked in the mist: the landscape of mammalian replication origins.The Journal of cell biology · 2015Review
- The hunt for origins of DNA replication in multicellular eukaryotes.F1000prime reports · 2015Review
- Chromatin structure and replication origins: determinants of chromosome replication and nuclear organization.Journal of molecular biology · 2014Review
- G4 motifs affect origin positioning and efficiency in two vertebrate replicators.The EMBO journal · 2014Article
- Activation of a human chromosomal replication origin by protein tethering.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The structure of replication origins in metazoans is only nominally similar to that in model organisms, such as Saccharomyces cerevisiae. By contrast to the compact origins of budding yeast, in metazoans multiple elements act as replication start sites or control replication efficiency. We first reported that replication forks diverge from an origin 5' to the human c-myc gene and that a 2.4-kb core fragment of the origin displays autonomous replicating sequence activity in plasmids and replicator activity at an ectopic chromosomal site. Here we have used clonal HeLa cell lines containing mutated c-myc origin constructs integrated at the same chromosomal location to identify elements important for DNA replication. Replication activity was measured before or after integration of the wild-type or mutated origins using PCR-based nascent DNA abundance assays. We find that deletions of several segments of the c-myc origin, including the DNA unwinding element and transcription factor binding sites, substantially reduced replicator activity, whereas deletion of the c-myc promoter P1 had only a modest effect. Substitution mutagenesis indicated that the sequence of the DNA unwinding element, rather than the spacing of flanking sequences, is critical. These results identify multiple functional elements essential for c-myc replicator activity.
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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.