Epigenetic Control of the Mitotic Cell Cycle
Lyle Armstrong in Epigenetics, 2020
A schematic representation of the mitotic cell cycle is shown in this chapter. Phosphorylation of histone H1 increases its ability to dissociate from the chromatin fiber. In the context of cell cycle progression, it is known that tethering of Cdc45-a protein associated with the transition from G1 to S phase-to a chromosomal locus promotes large-scale chromatin decondensation. When a cell divides, chromosomes need to reorganize into compact rod-shaped bodies to permit the segregation of their replicated sister chromatids to opposite spindle poles. A fascinating aspect of the mitotic cell cycle is that the pattern of histone modifications present in the genome of specific cell types is identical (for all practical purposes) before and after mitosis. Such epigenetic “memory” of the cell’s transcriptional profile is currently a very active area of investigation.
Side-effects, interactions and pharmacokinetics
Roger Mcfadden in Introducing Pharmacology, 2009
This chapter explains the cellular origins and pathophysiology of common cancers and the pharmacological action of anti-cancer drugs. Most anti-cancer drugs inhibit the cell division so the people need to understand the process of cell division in order to understand how these drugs work. An ideal anti-cancer drug would kill all cancer cells while leaving normal, healthy cells untouched but targeting the cancerous cells is difficult because differences from other body cells are small. The prednisolone is not an anti-cancer drug but it recruits resting cancer cells from G 0 phase into G 1 phase of the active cell cycle where they are targeted by other drugs in the R-CHOP regime. Anti-cancer drugs target cells that are dividing rapidly, with the intention of either stopping cell division or damaging the cell to the extent that it either self-destructs or is destroyed by the body's own immune cells.
Histone Interactions with DNA
Lubomir S. Hnilica in The Structure and Biological Function of Histones, 1972
Since histones are known to quantitatively restrict DNA transcription in vitro and, most likely, in vivo, many experiments have been reported in the literature concerning the specificity of interactions between DNA and basic proteins. The manner in which the DNA and histone fractions were brought together in vitro apparently affected the stability properties of the resulting complexes. The functional form of the chromosomal DNA in eukaryotes is associated with other macromolecules such as histones, nonhistone proteins, lipids or lipoproteins, RNA, etc. The composition of typical chromatin consists of almost equal proportions of DNA and histones and smaller amounts of nonhistone proteins and RNA. Since DNA at similar concentrations does not form cross-linked gels, the formation of gels by isolated chromatin in water must be due to its protein content. During the cell cycle of eukaryotic cells, the chromatin nucleoprotein assumes various states of condensation.
Lighting The Circle of Life: Fluorescent Sensors for Covert Surveillance of the Cell Cycle
Published in Cell Cycle, 2003
The cell cycle is the collective mechanism through which all of us develop, exist and in many cases, when it goes wrong, die. Despite enormous progress in unravelling the complexity of the cell cycle through intensive study over the past 100 years, development of new tools to analyse the process and associated cellular events has not kept pace. All standard cell cycle analysis methods preclude real time dynamic analysis of the cell cycle in live cells at single cell resolution. To address the needs of cell cycle investigations across a range of analysis platforms we are currently developing a range of cell cycle phase markers based on GFP expression controlled by well characterised cell cycle components to allow covert surveillance of the cell cycle in living cells.
MicroRNAs and cell cycle of malignant glioma
Published in International Journal of Neuroscience, 2016
Qing Ouyang, Lunshan Xu, Hongjuan Cui, Minhui Xu, Liang Yi
The control of malignant glioma cell cycle by microRNAs (miRNAs) is well established. The deregulation of miRNAs in glioma may contribute to tumor proliferation by directly targeting the critical cell-cycle regulators. Tumor suppressive miRNAs inhibit cell cycle through repressing the expression of positive cell-cycle regulators. However, oncogenic miRNAs promote the cell-cycle progression by targeting cell-cycle negative regulators. Recent studies have identified that transcription factors had involved in the expression of miRNAs. Transcription factors and miRNAs are implicated in regulatory network of glioma cell cycle, the deregulation of these transcription factors might be a cause of the deregulation of miRNAs. Abnormal versions of miRNAs have been implicated in the cell cycle of glioma. Based on those, miRNAs are excellent biomarker candidates and potential targets for therapeutic intervention in glioma.
Graded requirement for the spliceosome in cell cycle progression
Published in Cell Cycle, 2015
Zemfira Karamysheva, Laura A Díaz-Martínez, Ross Warrington, Hongtao Yu
Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.