The Experts below are selected from a list of 52428 Experts worldwide ranked by ideXlab platform
Ana Pombo - One of the best experts on this subject based on the ideXlab platform.
-
models of Chromosome Structure
Current Opinion in Cell Biology, 2014Co-Authors: Mario Nicodemi, Ana PomboAbstract:Understanding the mechanisms that control Chromosome folding in the nucleus of eukaryotes and their contribution to gene regulation is a key open issue in molecular biology. Microscopy and chromatin-capture techniques have shown that chromatin has a complex organization, which dynamically changes across organisms and cell types. The need to make sense of such a fascinating complexity has prompted the development of quantitative models from physics, to find the principles of Chromosome folding, its origin and function. Here, we concisely review recent advances in Chromosome modeling, focusing on a recently proposed framework, the Strings & Binders Switch (SBS) model, which recapitulates key features of Chromosome organization in space and time.
-
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
Journal of Cell Biology, 1998Co-Authors: Dean A Jackson, Ana PomboAbstract: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 ∼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.
-
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
Journal of Cell Biology, 1998Co-Authors: Dean A Jackson, Ana PomboAbstract: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.
-
Transcription factories and Chromosome Structure
Chromosomes Today, 1997Co-Authors: Ana Pombo, Francisco J. Iborra, Thomas A. Hughes, Dean A Jackson, John Mcmanus, Peter R. CookAbstract:Condensation is the hallmark of mitosis. Why, then, does the chromatin fibre not condense into the most compact form, a sphere? Why are chromatids cylindrical, and not spherical? What are the basic principles that determine the cylindrical shape?
Alexander V Strunnikov - One of the best experts on this subject based on the ideXlab platform.
-
smc proteins and Chromosome Structure
Trends in Cell Biology, 1998Co-Authors: Alexander V StrunnikovAbstract:The Structure of Chromosomes is largely determined by Chromosome-associated proteins. Members of the SMC (structural maintenance of Chromosomes) family play an important role in both prokaryotic and eukaryotic Chromosome Structure and dynamics. SMC proteins are involved in Chromosome condensation, sister-chromatid cohesion, sex-Chromosome dosage compensation, genetic recombination and DNA repair. There have been major advances recently in understanding the function of SMC proteins--including the identification of biochemical activities of SMC-containing protein complexes and the realization that individual SMC proteins might link seemingly unrelated aspects of chromosomal metabolism.
-
a direct link between sister chromatid cohesion and Chromosome condensation revealed through the analysis of mcd1 in s cerevisiae
Cell, 1997Co-Authors: Vincent Guacci, Douglas Koshland, Alexander V StrunnikovAbstract:Abstract The S. cerevisiae MCD1 (mitotic Chromosome determinant) gene was identified in genetic screens for genes important for Chromosome Structure. MCD1 is essential for viability and homologs are found from yeast to humans. Analysis of the mcd1 mutant and cell cycle–dependent expression pattern of Mcd1p suggest that this protein functions in Chromosome morphogenesis from S phase through mitosis. The mcd1 mutant is defective in sister chromatid cohesion and Chromosome condensation. The physical association between Mcd1p and Smc1p, one of the SMC family of chromosomal proteins, further suggests that Mcd1p functions directly on Chromosomes. These data implicate Mcd1p as a nexus between cohesion and condensation. We present a model for mitotic Chromosome Structure that incorporates this previously unsuspected link.
Andrew S Belmont - One of the best experts on this subject based on the ideXlab platform.
-
mitotic Chromosome Structure reproducibility of folding and symmetry between sister chromatids
Biophysical Journal, 2009Co-Authors: Yuri G Strukov, Andrew S BelmontAbstract:Mitotic Chromosome Structure and pathways of mitotic condensation remain unknown. The limited amount of structural data on mitotic Chromosome Structure makes it impossible to distinguish between several mutually conflicting models. Here we used a Chinese hamster ovary cell line with three different lac operator-tagged vector insertions distributed over an ∼1 μm Chromosome arm region to determine positioning reproducibility, long-range correlation in large-scale chromatin folding, and sister chromatid symmetry in minimally perturbed, metaphase Chromosomes. The three-dimensional positions of these lac operator-tagged spots, stained with lac repressor, were measured in isolated metaphase Chromosomes relative to the central chromatid axes labeled with antibodies to topoisomerase II. Longitudinal, but not axial, positioning of spots was reproducible but showed intrinsic variability, up to ∼300 nm, between sister chromatids. Spot positions on the same chromatid were uncorrelated, and no correlation or symmetry between the positions of corresponding spots on sister chromatids was detectable, showing the absence of highly ordered, long-range chromatin folding over tens of mega-basepairs. Our observations are in agreement with the absence of any regular, reproducible helical, last level of Chromosome folding, but remain consistent with any hierarchical folding model in which irregularity in folding exists at one or multiple levels.
-
mitotic Chromosome Structure and condensation
Current Opinion in Cell Biology, 2006Co-Authors: Andrew S BelmontAbstract:Mitotic Chromosome Structure has been the cell biology equivalent of a 'riddle, wrapped in a mystery, inside an enigma'. Observations that genetic knockout or knockdown of condensin subunits or topoisomerase II cause only minimal perturbation in overall Chromosome condensation, together with analysis of early stages of Chromosome condensation and effects produced by histone H1 depletion, suggest a need to reconsider textbook models of mitotic Chromosome condensation and organization.
-
Visualization of early Chromosome condensation: a hierarchical folding, axial glue model of Chromosome Structure
Journal of Cell Biology, 2004Co-Authors: Natashe Kireeva, Tatsuya Hirano, Margot Lakonishok, Igor I. Kireev, Andrew S BelmontAbstract:Current models of mitotic Chromosome Structure are based largely on the examination of maximally condensed metaphase Chromosomes. Here, we test these models by correlating the distribution of two scaffold components with the appearance of prophase Chromosome folding intermediates. We confirm an axial distribution of topoisomerase IIα and the condensin subunit, structural maintenance of Chromosomes 2 (SMC2), in unextracted metaphase Chromosomes, with SMC2 localizing to a 150–200-nm-diameter central core. In contrast to predictions of radial loop/scaffold models, this axial distribution does not appear until late prophase, after formation of uniformly condensed middle prophase Chromosomes. Instead, SMC2 associates throughout early and middle prophase chromatids, frequently forming foci over the Chromosome exterior. Early prophase condensation occurs through folding of large-scale chromatin fibers into condensed masses. These resolve into linear, 200–300-nm-diameter middle prophase chromatids that double in diameter by late prophase. We propose a unified model of Chromosome Structure in which hierarchical levels of chromatin folding are stabilized late in mitosis by an axial “glue.”
-
visualization of g1 Chromosomes a folded twisted supercoiled chromonema model of interphase chromatid Structure
Journal of Cell Biology, 1994Co-Authors: Andrew S Belmont, Kathy BruceAbstract:We have used light microscopy and serial thin-section electron microscopy to visualize intermediates of Chromosome decondensation during G1 progression in synchronized CHO cells. In early G1, tightly coiled 100-130-nm "chromonema" fibers are visualized within partially decondensed chromatin masses. Progression from early to middle G1 is accompanied by a progressive uncoiling and straightening of these chromonema fibers. Further decondensation in later G1 and early S phase results in predominantly 60-80-nm chromonema fibers that can be traced up to 2-3 microns in length as discrete fibers. Abrupt transitions in diameter from 100-130 to 60-80 nm along individual fibers are suggestive of coiling of the 60-80-nm chromonema fibers to form the thicker 100-130-nm chromonema fiber. Local unfolding of these chromonema fibers, corresponding to DNA regions tens to hundreds of kilobases in length, reveal more loosely folded and extended 30-nm chromatin fibers. Kinks and supercoils appear as prominent features at all observed levels of folding. These results are inconsistent with prevailing models of Chromosome Structure and, instead, suggest a folded chromonema model of Chromosome Structure.
Dean A Jackson - One of the best experts on this subject based on the ideXlab platform.
-
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
Journal of Cell Biology, 1998Co-Authors: Dean A Jackson, Ana PomboAbstract: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.
-
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
Journal of Cell Biology, 1998Co-Authors: Dean A Jackson, Ana PomboAbstract: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 ∼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.
-
Transcription factories and Chromosome Structure
Chromosomes Today, 1997Co-Authors: Ana Pombo, Francisco J. Iborra, Thomas A. Hughes, Dean A Jackson, John Mcmanus, Peter R. CookAbstract:Condensation is the hallmark of mitosis. Why, then, does the chromatin fibre not condense into the most compact form, a sphere? Why are chromatids cylindrical, and not spherical? What are the basic principles that determine the cylindrical shape?
Peter Fraser - One of the best experts on this subject based on the ideXlab platform.
-
Single-cell Hi-C reveals cell-to-cell variability in Chromosome Structure
Nature, 2013Co-Authors: Takashi Nagano, Yaniv Lubling, Eitan Yaffe, Amos Tanay, Thomas J. Stevens, Stefan Schoenfelder, Ernest D. Laue, Wendy Dean, Peter FraserAbstract:Large-scale Chromosome Structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on Chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging Chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X Chromosomes, to show that individual Chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell Chromosome Structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of Chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of Chromosomes, demonstrating how modular organization underlies dynamic Chromosome Structure, and how this Structure is probabilistically linked with genome activity patterns.