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The Role of Histone Deacetylases in Human Cancer - Coursework Example

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The paper "The Role of Histone Deacetylases in Human Cancer" highlights that if the western blot positivity for p21 proteins corresponds with the positivity in PCR assays, it can be inferred that the transcription of p21 mRNA is accompanied with the translation into p21 protein. …
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The Role of Histone Deacetylases in Human Cancer
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Download file to see previous pages The following essay summarizes the structure of chromatin with reference to the histones and discusses the post-translational modifications of these proteins.  The enzymes involved in acetylation/deacetylation of histones and the inhibitors of these enzymes are described in view of their applications in controlling human cancer.
The packaging unit of the chromatin is called nucleosome. The nucleosome is formed of a histone core of eight molecules of histones; two H2A, two H2B, two H3 and two H4. Each nucleosome consists of 1.75 superhelical turns (146 nucleotides length) of DNA wrapped around the core histone barrel-shaped octamers. The N-terminus of each octamer subunit is protruding free to be accessible for covalent modifications. A linker stretch of DNA (30 nucleotides in length) connects between the nucleosome cores and is covered by one molecule of histone H1 so as to close two turns of DNA (Figure 1).
Histones are basic non-heat coagulable proteins that are very rich in lysine and arginine (20-30%). Thus, they are positively charged at the physiological pH to bind the negatively charged DNA molecules. There are five types of histones; H1, H2A, H2B, H3 and H4 (ranging from 22-11 kDa, respectively). Histone proteins in the nucleosome have been assigned several dynamic regulatory roles induced by the reversible covalent modifications of their N-terminal tail, e.g., acetylation, methylation, ADP-ribosylation, ubiquitination and phosphorylation. The regulatory roles of histones include - control of the rate of gene expression (Induction/repression and silencing); chromosomal condensation and assembly during replication; and DNA repair. During assembly of the nucleosome, the flexible tails entwine with the DNA superhelices and bring them closer to the other histone-DNA complexes to stabilize the beaded structures (Luger and Richmond, 1998).
The organization of the 2 nm DNA double-strand in nucleosomes makes it look like beads-in-a-string that is called the 10 nm fibers. This fiber is then coiled again around a linear hollow axis as a helix with 6 - 7 nucleosomes per turn to form the solenoid 30 nm fiber (like the telephone cord).  ...Download file to see next pagesRead More
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