The Spiral Structure of Chromosomes

Manton, I.

doi:10.1111/j.1469-185x.1950.tb00770.x

Cited by 68 publications

(40 citation statements)

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“…It is likely, however, that even higher levels of chromatin packaging exist. It has been hypothesized that interphase chromatin may possess a coiled configuration (Manuelidis, 1990), although the experimental evidence was offered only for metaphase chromosomes, some of which had a coiled structure visualized by light and electron microscopy (Manton, 1950;Ohnuki, 1965;Rattner and Lin, 1985;Sumner, 1991). However, even for metaphase chromosomes, this concept remains debatable since coiling is not generally visible and was demonstrated only in small proportion of chromosomes.…”

Section: Discussionmentioning

confidence: 93%

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

et al. 2005

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Recurrent chromosomal rearrangements are common in cancer cells and may be influenced by nonrandom positioning of recombination-prone genetic loci in the nucleus. However, the mechanism responsible for spatial proximity of specific loci is unknown. In this study, we use an 18 Mb region on 10q11.2-21 containing the RET gene and its recombination partners, the H4 and NCOA4 (ELE1) genes, as a model chromosomal region frequently involved in RET/PTC rearrangements in thyroid cancer. RET/PTC is particularly common in tumors from children exposed to ionizing radiation. Using fluorescence in situ hybridization and three-dimensional microscopy, the locations of five different loci in this region were mapped in interphase nuclei of normal human thyroid cells. We show that RET and NCOA4 are much closer to each other than expected based on their genomic separation. Modeling of chromosome folding in this region suggests the presence of chromosome coiling with coils of B8 Mb in length, which positions the RET gene close to both, the NCOA4 and H4, loci. There was no significant variation in gene proximity between adult and pediatric thyroid cells. This study provides evidence for large-scale chromosome folding of the 10q11.2-21 region that offers a structural basis for nonrandom positioning and spatial proximity of potentially recombinogenic intrachromosomal loci.

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Section: Discussionmentioning

confidence: 93%

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

et al. 2005

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“…3 in references 18 and 27). This is a surprising result as no such chirality has previously been reported either in mitotic or polytene chromosome coiling (7,26). To demonstrate the asymmetry by an independent and more quantitative method, we have used the triple product, a standard vector operation, which has been used previously to analyze helices in proteins (9).…”

Section: Chromosome Coils Are Right-handedmentioning

confidence: 99%

Spatial organization of chromosomes in the salivary gland nuclei of Drosophila melanogaster.

Hochstrasser¹,

Mathog²,

Gruenbaum³

et al. 1986

The Journal of Cell Biology

252

221

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Abstract. Using a computer-based system for model building and analysis, three-dimensional models of 24Drosophila melanogaster salivary gland nuclei have been constructed from optically or physically sectioned glands, allowing several generalizations about chromosome folding and packaging in these nuclei. First and most surprising, the prominent coiling of the chromosomes is strongly chiral, with fight-handed gyres predominating. Second, high frequency appositions between certain loci and the nuclear envelope appear almost exclusively at positions of intercalary heterochromatin; in addition, the chromocenter is always apposed to the envelope. Third, chromosomes are invariably separated into mutually exclusive spatial domains while usually extending across the nucleus in a polarized (Rabl) orientation. Fourth, the arms of each autosome are almost always juxtaposed, but no other relative arm positions are strongly favored. Finally, despite these nonrandom structural features, each chromosome is found to fold into a wide variety of different configurations. In addition, a set of nuclei has been analyzed in which the normally aggregrated centromeric regions of the chromosomes are located far apart from one another. These nuclei have the same architectural motifs seen in normal nuclei. This implies that such characteristics as separate chromosome domains and specific chromosomenuclear envelope contacts are largely independent of the relative placement of the different chromosomes within the nucleus.E UKARYOTIC cells contain enormous lengths of DNA that must undergo considerable packing to fit inside the interphase nucleus. The packing is accomplished through multiple foldings of the DNA molecule within each chromosome and the folding of the chromosomes themselves inside the nucleus. This hierarchy of foldings is under several general constraints. First, the DNA must be available to regulatory factors and transcriptional machinery in such a way that readout of the genome can be precisely controlled. Second, the resident copies of DNA must be faithfully duplicated and repackaged with histones and other proteins; in dividing cells, the daughter helices must also be topologically resolved. Finally, nuclear division depends on a number of tightly orchestrated events: condensation of chromatin into compact chromosomes, dissolution of the nuclear envelope, movement of chromosomes to a central plate with subsequent splitting of daughter chromatids toward opposite poles, decondensation of daughter chromosomes, and reassembly of the nuclear envelope around them.Despite the interest in elucidating the means by which cells accommodate these constraints and package their genomes, only a meager sketch of higher order structures can currently be claimed. Beyond the level of the 10-nm nucleosomal fiber, little.consensus has been reached. This is particularly true of the highest level of chromosome organization, the threedimensional arrangement of chromosomes in the interphase nucleus. For reviews, see references 13 and 21.The giant ...

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“…A scaffold of proteins form an axis along which solenoidal chromatin loops are folded into rosettes, which then coalesce to form a sausage-shaped chromonema Marsden and Laemmli, 1979;Johnson, 1979, 1980;Earnshaw and Laemmli, 1983;Earnshaw, 1988). The metaphase chromosome consists of a folded or coiled chromonema (Manton, 1950). In a more recent model of chromosome organization, chromatin is folded into fibers around the central axis, which acts as a "glue" (Kireeva et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Analysis of Chromosome Condensation inSaccharomyces cerevisiae

Vas

Andrews

Matesky

et al. 2007

MBoC

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Although chromosome condensation in the yeast Saccharomyces cerevisiae has been widely studied, visualization of this process in vivo has not been achieved. Using Lac operator sequences integrated at two loci on the right arm of chromosome IV and a Lac repressor-GFP fusion protein, we were able to visualize linear condensation of this chromosome arm during G2/M phase. As previously determined in fixed cells, condensation in yeast required the condensin complex. Not seen after fixation of cells, we found that topoisomerase II is required for linear condensation. Further analysis of perturbed mitoses unexpectedly revealed that condensation is a transient state that occurs before anaphase in budding yeast. Blocking anaphase progression by activation of the spindle assembly checkpoint caused a loss of condensation that was dependent on Mad2, followed by a delayed loss of cohesion between sister chromatids. Release of cells from spindle checkpoint arrest resulted in recondensation before anaphase onset. The loss of condensation in preanaphase-arrested cells was abrogated by overproduction of the aurora B kinase, Ipl1, whereas in ipl1-321 mutant cells condensation was prematurely lost in anaphase/telophase. In vivo analysis of chromosome condensation has therefore revealed unsuspected relationships between higher order chromatin structure and cell cycle control. INTRODUCTIONAccurate chromosome segregation during mitosis is facilitated by the resolution of chromosomes into compact structures. From the level of the nucleosome, chromatin undergoes several changes in organization (Earnshaw, 1988;Filipski et al., 1990). A scaffold of proteins form an axis along which solenoidal chromatin loops are folded into rosettes, which then coalesce to form a sausage-shaped chromonema Marsden and Laemmli, 1979; Johnson, 1979, 1980;Earnshaw and Laemmli, 1983;Earnshaw, 1988). The metaphase chromosome consists of a folded or coiled chromonema (Manton, 1950). In a more recent model of chromosome organization, chromatin is folded into fibers around the central axis, which acts as a "glue" (Kireeva et al., 2004). In both of these models, the protein scaffold is proposed to condense linearly during mitosis.The mitotic scaffold was first observed in histone-depleted mammalian chromosomes and components of this protein scaffold have been of considerable interest (Adolphs et al., 1977;Paulson and Laemmli, 1977). In higher eukaryotes, the process of condensing chromosomes before anaphase requires a protein scaffold comprised of at least condensin and topoisomerase II (Earnshaw et al., 1985;Gasser et al., 1986;Adachi et al., 1991;Saitoh et al., 1994;Gimenez-Abian et al., 1995;Hirano et al., 1997;Maeshima and Laemmli, 2003). Condensin is a five-subunit complex that was first identified in Xenopus egg extracts (Hirano, 2005). Homologues of mitotic scaffold proteins are present in all eukaryotes (reviewed in Hirano, 2005). In the budding yeast Saccharomyces cerevisiae, homologues of the condensin complex, encoded by SMC2, SMC4, YCG1, YCS4, and BRN...

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The Spiral Structure of Chromosomes

Cited by 68 publications

References 69 publications

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

Spatial organization of chromosomes in the salivary gland nuclei of Drosophila melanogaster.

In Vivo Analysis of Chromosome Condensation inSaccharomyces cerevisiae

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