Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells.
Dean A. Jackson,Ana Pombo +1 more
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TLDR
It is proposed that the coordinated replication of related groups of replicons, that form stable replicon clusters, contributes to the efficient activation and propagation of S phase in mammalian cells.Abstract:
In proliferating cells, DNA synthesis must be performed with extreme precision. We show that groups of replicons, labeled together as replicon clusters, form stable units of chromosome structure. HeLa cells were labeled with 5-bromodeoxyuridine (BrdU) at different times of S phase. At the onset of S phase, clusters of replicons were activated in each of approximately 750 replication sites. The majority of these replication "foci" were shown to be individual replicon clusters that remained together, as stable cohorts, throughout the following 15 cell cycles. In individual cells, the same replication foci were labeled with BrdU and 5-iododeoxyuridine at the beginning of different cell cycles. In DNA fibers, 95% of replicons in replicon clusters that were labeled at the beginning of one S phase were also labeled at the beginning of the next. This shows that a subset of origins are activated both reliably and efficiently in different cycles. The majority of replication forks activated at the onset of S phase terminated 45-60 min later. During this interval, secondary replicon clusters became active. However, while the activation of early replicons is synchronized at the onset of S phase, different secondary clusters were activated at different times. Nevertheless, replication foci pulse labeled during any short interval of S phase were stable for many cell cycles. We propose that the coordinated replication of related groups of replicons, that form stable replicon clusters, contributes to the efficient activation and propagation of S phase in mammalian cells.read more
Citations
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Journal ArticleDOI
Chromosome territories, nuclear architecture and gene regulation in mammalian cells.
TL;DR: The emerging view is that chromosomes are compartmentalized into discrete territories and the location of a gene within a chromosome territory seems to influence its access to the machinery responsible for specific nuclear functions, such as transcription and splicing.
Nuclear architecture and gene regulation in mammalian cells
TL;DR: The emerging view is that chromosomes are compartmentalized into discrete territories, and the location of a gene within a chromosome territory seems to influence its access to the machinery responsible for specific nuclear functions, such as transcription and splicing.
Journal ArticleDOI
Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11
TL;DR: Using single-molecule DNA fiber analysis, it is shown that nascent replication tracts created before fork stalling with hydroxyurea are degraded in the absence of BRCA2 but are stable in wild-type cells.
Journal ArticleDOI
Differences in the localization and morphology of chromosomes in the human nucleus
TL;DR: It is demonstrated that the distribution of genomic sequences between chromosomes has implications for nuclear structure and the findings are discussed in relation to a model of the human nucleus that is functionally compartmentalized.
Journal ArticleDOI
Topologically associating domains are stable units of replication-timing regulation
Benjamin D. Pope,Tyrone Ryba,Vishnu Dileep,Feng Yue,Weisheng Wu,Olgert Denas,Daniel L. Vera,Yanli Wang,R. Scott Hansen,Theresa K. Canfield,Robert E. Thurman,Yong Cheng,Günhan Gülsoy,Jonathan H. Dennis,Michael Snyder,John A. Stamatoyannopoulos,James Taylor,Ross C. Hardison,Tamer Kahveci,Bing Ren,David M. Gilbert +20 more
TL;DR: It is demonstrated that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replicationdomain boundaries, largely accounting for the previously reported lack of alignment.
References
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A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei
TL;DR: Analysis of DNA MTase-beta-galactosidase fusion proteins has shown that association with replication foci is mediated by a novel targeting sequence located near the N-terminus of DNAMTase.
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Isolation and characterisation of a yeast chromosomal replicator.
TL;DR: A yeast DNA sequence that behaves as a chromosomal replicator, ars1 (autonomously replicating sequence), has been isolated and allows autonomous replication of all co-linear DNA.
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On the mechanism of DNA replication in mammalian chromosomes
Joel A. Huberman,Arthur D. Riggs +1 more
TL;DR: It is found that the long fibers of which chromosomal DNA is composed are made up of many tandemly joined sections in each of which DNA is replicated at a fork-like growing point.
Journal ArticleDOI
Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy.
TL;DR: The results confirm the generally accepted theory that DNA is replicated coordinately in a specific temporal order during the S-phase and conclude that replicon clusters located in the same region are replicated in the the same relatively short period of time.
Journal ArticleDOI
A fixed site of DNA replication in eucaryotic cells
TL;DR: Electron microscopic autoradiography shows that, as with intact nuclei, sites of DNA replication are distributed throughout the nuclear matrix, and a fixed site of DNA synthesis is proposed in which DNA replication complexes are anchored to thenuclear matrix.
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