First interactive model of human cell division

Mitosis — how one cell divides and becomes two — is one of the fundamental processes of life. Researchers have now produced an interactive map of proteins that make our cells divide, allowing users to track exactly where and in which groups the proteins drive the division process forward. (Mehr in: Cancer News — ScienceDaily)

Studying mitosis‘ structure to understand the inside of cancer cells

Cell division is an intricately choreographed ballet of proteins and molecules that divide the cell. During mitosis, microtubule-organizing centers assemble the spindle fibers that separate the copying chromosomes of DNA. While scientists are familiar with MTOCs‘ existence and the role they play in cell division, their actual physical structure remains poorly understood. Researchers are now trying to decipher their molecular architecture. (Mehr in: Cancer News — ScienceDaily)

How cells rebuild after mitosis

New research has revealed how cells rebuild their nucleus and organize their genome when they divide, a discovery which could have major implications for understanding cancer and degeneration. (Mehr in: Cancer News — ScienceDaily)

Cancer drug stimulates tripolar mode of mitosis

Taxanes inhibit cell division and make cancer cells sensitive to radiation therapy. A current study has investigated the underlying mechanisms of this action – and which biomarkers may be useful for predicting the success of therapy. (Mehr in: Cancer News — ScienceDaily)

Cancer Drug Stimulates Tripolar Mode of Mitosis

Taxanes inhibit cell division and make cancer cells sensitive to radiation therapy. A current study has investigated the underlying mechanisms of this action – and which biomarkers may be useful for predicting the success of therapy. The study, published in the journal ‘Oncogene’, was carried out within the framework of the Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer at Helmholtz Zentrum München and Munich University Hospital. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

Mitosis study finds potential cancer target

By drilling down to the atomic level of how specific proteins interact during cell division, or mitosis, a team of scientists has found a unique new target for attacking cancer. (Mehr in: Cancer News — ScienceDaily)

Biomolecular force generation based on the principle of a gas spring

The mechanical basis of mitosis has only been understood in fragments so far. Scientists at Technische Universität Dresden have now been able to add another piece to the puzzle of cell biological mechanisms, as they report in the latest issue of the renowned scientific journal “Cell” on March 5, 2015. (Mehr in: Pressemitteilungen – idw – Informationsdienst Wissenschaft)

A new theory of the origin of cancer: quantum coherent entanglement, centrioles, mitosis, and differentiation

Low non-specific, low intensity laser illumination (635, 670 or 830 nm) apparently enhances centriole replication and promotes cell division, what is the opposite of a desired cancer therapy. In the contrary, centrioles are sensitive to coherent light. Then higher intensity laser illumination – still below heating threshold – may selectively target centrioles, impair mitosis and be a beneficial therapy against malignancy. If centrioles utilize quantum photons for entanglement, properties of centrosomes/centrioles approached more specifically could be useful for therapy. Healthy centrioles for a given organism or tissue differentiation should then have specific quantum optical properties detectable through some type of readout technology. An afflicted patient’s normal cells could be examined to determine the required centriole properties which may then be used to generate identical quantum coherent photons administered to the malignancy. In this mode the idea would not be to destroy the tumor – relatively low energy lasers would be used – but to “reprogram” or redifferentiate the centrioles and transform the tumor back to healthy well differentiated tissue.

Hameroff, SR (2004) A new theory of the origin of cancer: quantum coherent entanglement, centrioles, mitosis, and differentiation. BioSystems 77, 119–136

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P <0.001. 3D-SIM, three-dimensional structured illumination microscopy; CDC, chromatin domain cluster; DAPI, 4',6-diamidino-2-phenylindole; FISH, fluorescence in situ hybridization; IC, interchromatin compartment; Xa, active X chromosome; Xi, inactive X chromosome. Smeets et al. Epigenetics & Chromatin 2014 7:8   doi:10.1186/1756-8935-7-8
3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P Smeets et al. Epigenetics & Chromatin 2014 7:8 doi:10.1186/1756-8935-7-8

Daniel Smeets, Yolanda Markaki, Volker J Schmid, Felix Kraus, Anna Tattermusch, Andrea Cerase, Michael Sterr, Susanne Fiedler, Justin Demmerle, Jens Popken, Heinrich Leonhardt, Neil Brockdorff, Thomas Cremer1, Lothar Schermelleh and Marion Cremer

Abstract

Background

A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs).

Results

We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an ‘autosomal Barr body’ with less compacted chromatin and incomplete RNAP II exclusion.

Conclusions

3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi.

Continue reading „Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci“