Nucleohistone complex

A study has been made of the DNA secondary structure induced by the various nucleohistone complexes 342). The interaction of calf thymus DNA with the anticancer drug Cisplatin in water and heavy water has been studied. The carbonyl bands at 1710 and 1686 cm-1 of the control DNA disappear and shift to lower frequencies in the spectra of the products of the reaction. The drug induces a reorganization of the water molecules and the DNA structure is modified 340). 

Salt bridges between positively charged basic amino acid side chains of histones and the negatively charged DNA phosphates play a major role in stabilizing the DNA-histone complex. Indeed, treatment of chromatin with concentrated NaCl (1-2 m), which is known to disrupt electrostatic bonds, causes a complete dissociation of DNA and histone in the nucleohistone complex. 

Computational studies on molecular subunits of the nucleohistone complex indicate that the binding strength of a single hydrogen bond... 

After dissociation of nucleohistone into DNA and histone in concentrated NaCl solutions, the nucleohistone complex can be restored by interaction between DNA and histone in dilute salt... 

Chaires JB, Herrera JE, Waring MJ (1990) Preferential binding of daunomycin to 5-ATCG and 5-ATGC sequences revealed footprinting, titration experiment. Biochemistry 29 6145-6153 Chakrabarti S, Mahmood A, Kassis AI, Bump EA, Jones AG, Makrigiorgos GM (1996) Generation of hydroxyl radicals by nucleohistone-bound metal-adriamycin complexes. Free Radic Res... 

Dds is the inter-duplex separation for complexes of MX-DNA. Dds is calculated from the apparent transfer distance, Da(l ), which is increased by transfer between duplexes and the actual transfer distance along one duplex, Di(l ), via Eq. 10, assuming Di(l ) is the same for both MX-DNA and MX-DNA solid complexes at similar hydration states. All are calculated assuming n= 6 except MX-nucleohistone for which n was assumed to be 4.5... 

It will be shown below that alkyl radicals add predominantly at the C(6)-positions of the pyrimidines and, when products as shown above are found after OH-attack in very complex systems such as nucleohistones (e.g., Gajewski et al. 1988 Dizdaroglu and Gajewski 1989 Dizdaroglu et al. 1989 Gajewski and Dizd-aroglu 1990) or Thy dimers in polydeoxythymidylic acid (Karam et al. 1986), it cannot be fully excluded that they are formed via the trivial two-radical recombination mechanism. 

Binding between DNA and poly-L-lysine at pH 7 was monitored at various molar ratios of the complex components by measurement of ORD changes in the range 220 to 360 nm. These changes could be compared with those occurring in DNA-protein complexes (see below, nucleohistones). Possible interpretations included tilting of the bases... 

CD spectra (200—350 nm) of calf thymus chromatin were compared with those of pure DNA in solution. Some of the differences observed (above approximately 250 nm) were attributed to conformational changes in the bound DNA, in which a large tilting of the bases may occur [(373) and refs, cited therein]. Previously, similar conclusions had been reached on the basis of ORD measurements on native nucleohistone and on nucleohistone dissociated either fully or partially into DNA and histone [(374) see also (375—379)]. CD studies on the state of DNA in native and partially deproteinized gander erythrocyte chromatin and of complexes of ethidium bromide with these systems were reported (380). 

Each prokaryotic chromosome consists of a supercoiled circular DNA molecule com-plexed to a protein core. Each eukaryotic chromosome consists of a single linear DNA molecule that is complexed with histones to form nucleohistone. 

Each eukaryotic chromosome is composed of nucleohistone, a complex formed by winding a single DNA molecule around a histone octomer to form a nucleosome. The DNA of mitochondria and chloroplasts is similar to the chromosomes found in prokaryotes. 

Histones occur in the chromosomes of organisms with genuine cell nuclei, for example, in the chromosomes of the thymus gland. The biological function of histones is largely unknown. They probably regulate replication or transcription. Histones are complexed with nucleic acids (nucleohistones) in organisms. 

Isolated nuclei are highly permeable to histones, protamines and other biological macromolecules, whereas ATP and Na become tightly bound. The chief components of isolated and disrupted nuclei are DNA-histone complexes (nucleohistones), ribonucleic acids and poorly soluble acidic proteins (residual proteins). Nuclei also contain high concentrations of an arginase and an adenosine S -phosphata e of unknown function. 

Despite the vast number of chemical and physical experiments, the available information is still insufficient to explain the detailed structiu e of the nucleohistones, with the exception of several DNA-repressor protein complexes. Some general tendencies, however, have been found the a-helix conformation of the polypeptides is predominant in histones, as has been shown by ORD experiments lysine-rich histones mainly occupy the major groove of B-DNA,< > while protamines are bound to DNA in the minor groove (for further details see Otto et alP ). 

A more conclusive answer to this and the other problems noted above can only be given by further theoretical investigations of the nucleohistones. On the one hand, the model systems must be improved by constructing a polypeptide helix that fits into the major groove of B-DNA and, at the same time, takes into account the amino-acid side chains. This last improvement, of course, has to be paralleled by the introduction of chemical aperiodicity in the DNA helix. On the other hand, a more realistic system can be approached step by step by including the influence of water surrounding the complex (more details can be found in Otto et alP° ). 

Littau and co-workers (1965) studied the chromatin structure of thymus lymphocytes by biochemical and electron-microscopic methods. They found that nucleohistone chromatin masses consist of two types of complexes compact and diffuse. The formation of compact complexes, as they showed, is associated with the lysine-rich histone, which forms cross-linkages between the DNA strands. The diffuse histone, in which synthesis of messenger RNA mainly takes place, has no such cross-linkages. It contains arginine-rich histone which is linked to DNA along its strands. 

However, in their attempt to find such an RNA—histone complex in a number of animal tissues, Commerford and Delihas (1966) were unable to confirm Bonner s findings exactly. In pea nucleohistone about 100 RNA—histone nucleotides were present for every thousand DNA nucleotides. In nucleohistone of the liver and intestinal mucous membrane only two RNA—histone nucleotides were present per thousand DNA nucleotides. Commerford and Delihas consider that this ratio alone is insufficient ground for assigning to this RNA fraction the role of a specific carrier of repressors. 

It is known that nucleohistone is to some extent soluble in pure water at 5 °C (Carter and Hall, 1940) or in a very dilute salt solution (Zubay and Doty, 1959 0.7 mM potassium phosphate buffer, pH 6.8) in an undissociated form (Carter, 1941 Zubay and Doty, 1959) and can be extracted by careful homogenization with pure water after adequate pretreatment of material. However, it is not clear with nucleo-protoamine whether the same procedure can be applied to the extraction and purification of the complex with high yield and with reproducibility. 

Bontemps, J. Houssier, C. Fredericq, E. Physicochemical study of the complexes of 33258 Hoechst with DNA and nucleohistone. 

Chakrabarti, S. Mahmood, A. Kassis, A. 1. Bump, E. A. Jones, A. G. Makrigiorgos, G. M. Generation of hydroxyl radicals by nucleohistone-bound metal-adriamycin complexes. Free Radical Res. 1996, 25, 207-220. 

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