Nonhistone Proteins and Nuclear Matrix Structures
Isaac Bekhor, Carol J. Mirell, C. C. Liew in Progress in Nonhistone Protein Research, 1985
Whether a microtrabeculae-like structure does exist in the nuclear interior remains to be known. As in the cytoplasm, it is possible that nucleoprotein aggregation is produced by the chemicals and treatments to which the nucleus is exposed in order to solubilize DNA, RNA, and histones. At the present time, it is unclear whether the proteinaceous nuclear network results from such manipulations. We intend here to critically evaluate this topic and the current concepts about the nature of nuclear matrix. In addition, since it is usually assumed that nuclear envelope, lamina, and pore complexes are matrix components, we are discussing them in the general context of the nuclear structures that are obtained after whole nuclei are DNA- and histone-depleted. Ultimately, nuclear matrix will be explicable only when biochemistry and physiology are integrated with morphology. At present, what is lacking is sound biochemistry, but despite this shortcoming, recent evidence of nucleoproteins that can be cross-linked through sulfhydryl groups, bind metal ions, and form polymers may further our understanding of the nature of the nuclear matrix.
Atypical Teratoid / Rhabdoid Tumors – AT/RT
David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack in Brain and Spinal Tumors of Childhood, 2020
At the core of rhabdoid tumor pathogenesis lie mutations of epigenetic regulators, i.e., the core protein of the chromatin-remodeling complex SWI/SNF, SMARCB1. Chromatin, the nucleoprotein material of a chromosome, plays an important role in gene expression and is modified through movement, dissociation, or reconstitution. The basic unit of chromatin is made of 146 basepairs of DNA wrapped around an octamer of histone proteins which in their assembly are termed the nucleosome.23 Changes of the nucleosome are mediated by the action of different multiprotein chromatin remodelers. SWI/SNF is a major player in altering chromatin structure by ATP-dependent disruption of histone–DNA interactions and unpacking dense, complex, tertiary structures. The SWI/SNF complex plays an important role in the regulation of critical cellular processes such as cell cycle progression, programmed cell death, differentiation, gene transcription, and DNA repair.24–26
Histone Interactions with DNA
Lubomir S. Hnilica in The Structure and Biological Function of Histones, 1972
Many physicochemical and biological properties of chromatin or nucleoprotein are the direct consequence of DNA interaction with histones. It is clear that such interactions are essential to the very existence of chromatin. The other macromolecular components frequently found in chromatin (e.g., nonhistone proteins, RNA, etc.) contribute refinements and individuality to the basic structure, as furniture creates the individuality of a house. The electrostatic nature of the interactions permits partial or complete dissociation of the DNA and histones in chromatin. Hence, studies based on gradual dissociation can determine what structural and other constraints histones impose upon the DNA in chromatin.
In vitro cytotoxicity of polyphenols from Datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets
Published in Drug and Chemical Toxicology, 2020
Elham Chamani, Roshanak Ebrahimi, Khatereh Khorsandi, Azadeh Meshkini, Asghar Zarban, Gholamreza Sharifzadeh
Studies have shown that DNA is a pharmacological target of many of the drugs currently in clinical use or in advanced clinical trials (Hurley and Boyd 1988, Sirajuddin et al. 2013). In the eukaryotes, nuclear DNA interacts with histone proteins and forms a nucleoprotein complex known as chromatin. Chromatin arranges the nuclear genome into a restricted volume. The first level of chromatin organization consists of DNA-folding around histone proteins to shape the fundamental unit of the chromatin, the nucleosome (Hübner et al. 2013). In a nucleosome, 147 bp of DNA are enfolded in an octamer with two copies of four core histone proteins (H2A, H2B, H3, and H4) (Nair and Kumar 2012). As a linker histone, histone H1 surrounds the chromatosome by protecting the internucleosomal linker DNA near the nucleosome entry-exit point (Dixon et al. 2016, Kalashnikova et al. 2016).
Recent advances in targeting protein arginine methyltransferase enzymes in cancer therapy
Published in Expert Opinion on Therapeutic Targets, 2018
Emily Smith, Wei Zhou, Polina Shindiapina, Said Sif, Chenglong Li, Robert A. Baiocchi
Virtually every nucleated cell of the human body contains an identical copy of the human genome. While each cell is intrinsically similar, the ability of a cell to differentiate and specialize is essential to normal embryonic development and survival of the organism. Our genome encodes the full repertoire of genes shared by all humans, but it is the coordinated expression of specified sets of genes that determines the differentiation and commitment of a cell to a distinct lineage. This controlled expression is regulated not by direct changes to the DNA sequence, but by a complex assortment of post-translational modifications that alter nucleoprotein–DNA interactions and ultimately drive changes in gene expression. The field of epigenetics studies chemical modifications of DNA and chromatin that set a dynamic stage to affect cellular phenotype, without changing genotype [1].
Investigational PARP inhibitors for the treatment of biliary tract cancer: spotlight on preclinical and clinical studies
Published in Expert Opinion on Investigational Drugs, 2021
Rutika Mehta, Anthony C Wood, James Yu, Richard Kim
BRCA1/2 mutations are reported in up to 5.0% of all BTCs with BRCA2 mutations more frequently reported in GBCs [5,13,28]. Both BRCA1 and BRCA2 are involved in the HR repair (hereafter referred to as HRR) process, which plays a major role in DSB repair. A DSB is detected by an MRN complex comprised of the meiotic recombination 11 homologue A (MRE11A)-Nijmegen breakage syndrome 1 (NSB1)-RAD50. BRCA1 now aids in the resection of 5ʹ DNA on either side of DSB, thus exposing single-strand DNA (ssDNA). With the help of BRCA2, DNA recombinase RAD51 is localized to the ssDNA. This RAD51 bound to DNA forms a nucleoprotein that initiates the homologous repair process. With the help of ligases and endonucleases, a successful HRR is completed. When HRR fails, such as when homologous DNA is unavailable, DNA is repaired by end joining, which usually results in DNA deletions. If these deletions occur is crucial tumor suppressor genes, then these lead to tumorigenesis [21]. In vitro studies have shown that mouse cell lines lacking Brca1 or Brca2 have enhanced use of NHEJ, and this leads to higher frequency of DNA deletions [29].
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