Nonhistones

The DNA in a eukaryotic cell nucleus during the interphase between cell divisions exists as a nucleoprotein complex called chromatin. The proteins of chromatin fall into two classes histones and nonhistone chromosomal proteins. 

Chromatin consists of very long double-stranded DNA molecules and a nearly equal mass of rather small basic proteins termed histones as well as a smaller amount of nonhistone proteins (most of which are acidic and... 

When the histone octamer is mixed with purified, double-stranded DNA, the same x-ray diffraction pattern is formed as that observed in freshly isolated chromatin. Electron microscopic studies confirm the existence of reconstituted nucleosomes. Furthermore, the reconsti-mtion of nucleosomes from DNA and histones H2A, H2B, H3, and H4 is independent of the organismal or cellular origin of the various components. The histone HI and the nonhistone proteins are not necessary for the reconstitution of the nucleosome core. 

Most of the DNA of animal cells is found in the nucleus, where DNA is the major constituent of the chromosomes. On the other hand, most of the RNA is located in the cytoplasm. Nuclear DNA exists as a thin, double helix only 2 nm wide. The double helix is folded and complexed with protein to form chromosomal strands approxim-ately 100 to 200 nm in diameter. Each chromosome contains a single DNA duplex. The human chromosomes vary in size the smallest contains approximately 4.6 X 10 base pairs of DNA, and the largest 2.4 X 10 base pairs. In contrast, the Escherichia coli chromosome has 4.5 x 106 base pairs. The DNA of die chromosomes is tightly packed and associated with both histone and nonhistone proteins. 

The primary Junction of the nucleosomes is to condense DNA. Further condensation of nucleosome DNA requires nonhistone nuclear proteins. These proteins make up a scaffoldlike structure around an additional helix consisting of coiled nucleosomes. This produces a structure that resembles a solenoid, with six nucleosome subunits per turn. The solenoid structure can form large loops that give additional structure to the incipient chromosome. 

The nucleus contains a large number of proteins other than histones. These so-called nonhistone proteins may or may not be tightly associated with the chromosomes. For example, the nucleus contains enzymes associated with the synthesis of RNA and DNA these are nonhistone proteins, but they are not part of the structure of chromosomes. One group of nonhistone proteins are the high mobility group (HMG) proteins, named for their rapid movement on polyacryl-amide gel electrophoresis. The HMG proteins, but not histone HI, are associated with the chromatin that is most active in RNA synthesis. 

Reeves, R., and Nissen, M.S. (1993) Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles./. Biol. Chem. 268, 21137-21146. 

Histones and nonhistone nuclear proteins Ribosomal protein S6 elF (eukaryotic initiation factor) eEF (eukaryotic elongation factor)... 

All nuclear receptors have sequences known as domains of nuclear location (Picard et al. 1987). These sequences, rich in arginine and lysine, confer upon the many proteins that contain them the capacity to bind to nonhistone nuclear proteins. Receptors have up to four of these sequences, whose cooperation is necessary for nuclear location. When these sequences are exposed, the receptor... 

A 35- to 40-fold incorporation (relative to other fractions) of labelled mercury into a nonhistone fraction of rat kidney nuclei has been reported [44]. By using flameless atomic absorption, a 12 to 15-fold enrichment of mercury was found in the euchromatin fraction of mouse liver nuclei [45, 46]. Mercury was not detected in the inactive heterochromatin. 

While studying the binding of mercury by chromatin of rats injected with mercuric chloride, the nonhistone chromatin proteins in rat and kidney cell nuclei were shown to be mainly responsible for the mercury deposition [43]. The mercury-binding nonhistone proteins were found to be heterogeneous by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. 

In isolated nuclei from rat liver and kidney, Ni2 + was bound to chromatin, polynucleosomes and to deproteinized DNA [339]. Ni2+ directly interacted with stable binding sites on the DNA molecule in chromatin and was associated with histone and nonhistone nuclear proteins [339, 340]. 

Nickel sulphate in peripheral blood T lymphocytes gave a marked increase of 32P label into nonhistone proteins [ 109], especially in the 30-40 kDa region. It was postulated that the increase in nuclear protein phosphorylation probably reflected an activation of the lymphocytes. 

Nickel chloride has been reported to induce DNA strand breaks in CHO cells [435] in a concentration, which did not significantly injure normal cellular division, and DNA-protein cross-links, which were concentration- and time-dependent and preferentially occurred in cells in the late S phase of the cell cycle [436], The nickel cross-linked proteins included nonhistone chromatin proteins, nonhistone DNA-binding proteins and a 30 kDa protein that comigrated electrophoretically with histone HI. Moreover, blocking of cell growth in S phase [249] and induction of DNA repair synthesis in CHO cells [437] and reduction in the fidelity of DNA synthesis [438, 439], have been reported. 

High mobility group (HMG) proteins are a family of small nonhistone chromatin-associated proteins which recognize structural distortions in DNA (11, 74, 75). Several NMR structures of HMG domains have been determined (76-78). High mobility group 1 (HMG1) box A... 

Chromatin The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH]... 

Goldknope, I. L. and Busch, H. Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proc. Natl. Acad. USA, 1977, 74, 864-868. 

Szabo C (1998) Role of poly(ADP-ribose)synthetase in inflammation. Eur J Pharmacol 350 1-19 Tanuma S, Johnson GS (1983) ADP-ribosylation of nonhistone high mobility group proteins in intact cells. J Biol Chem 258 4067-4070... 

Pehrson JR, Fried VA (1992) MacroH2A, a core histone containing a large nonhistone region. Science 257 1398-1400... 

Abstract Post-translational modifications of nonhistone proteins play a significant role in... 

Figure 1. Mechanistic effect of acetylation/deacetylation of histones and nonhistones on chromatin stracture.(a) Acetylation of non-histone proteins results in transcriptional activation (b) Acetylation of ORCl by HBOl is important for replication, (c) Acetylation of newly synthesized...

Reversible acetylation of histone and nonhistone proteins play key role in maintaining cellular homeostasis. In this following section we shall discuss about the physiological significances of acetylation and deacetylation of different classes of nonhistone proteins. 

Figure 3. Role of nonhistone protein acetylation in maintaining cellular homeostasis- mis-regulation and disease connection (a) Acetylation of nonhistone proteins are associated with active or repressed chromatin architecture as guided by suitable cellular signals for maintenance of gene expression. Misreg-ulation of HAT function leads to diseased state, where chromatin architecture is altered than under normal condition. In a parallel way the posttranslational modification status of these proteins may act as versatile tool to diagnose the various stages of disease manifestation e.g. probable involvement of acetylated NPMl modulating its stress response function can lead us to use it as a marker for various disease states, (b) Acetylation of nonhistone proteins in connection to diseases like Cancer, AIDS, Diabetes and others. (See Colour Plate 14.)...

Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of nonhistone proteins. Gene 363 15-23... 

Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M (2002) Increased mitotic phosphorylation of histone H3 attributable to AIM-l/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 62(18) 5168-5177 Paulson JR, Taylor SS (1982) Phosphorylation of histones 1 and 3 and nonhistone high mobihty group 14 by an endogenous kinase in HeLa metaphase chromosomes. J Biol Chem 257(11) 6064—6072 Petersen J, Paris J, Wilier M, Philippe M, Hagan IM (2001) The S. pombe aurora-related kinase Arkl associates with mitotic structures in a stage dependent manner and is required for chromosome segregation. J Cell Sci 114(Pt 24) 4371 384... 

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