[Relaxation of DNA-protein interactions in mouse lymphoblastic leukemic cells exposed to antineoplastic agents]. / Oslablenie DNK-belkovykh vzaimodeistvii v kletkakh leikoznykh limfoblastov myshei pod vliianiem nekotorykh protivoopukholevykh agentov.

It has been demonstrated by nucleoproteid-celite chromatography that 1-nitroso-1-methylurea, potassium cyanate and prospidin reduce DNA-protein interactions in chromatin of cell cultures from LL mice with lymphoblastic leukemia.

[Changes in RNA synthesis induced by n-methyl-nitrosourea]. / Izmeniia v sinteze RNK, vyzyvaemye N-metil-N-nitrozomochevinoi.

N-methyl- and N-nitrosourea (NMU) methylate and carbamoylate DNA, RNA and chromatin proteins. The paper is concerned with an analysis of the MNU-induced changes in the synthesis of RNA in isolated nuclei, chromatin, and in protein-free DNA. It was found that NMU decreases the rate of the RNA synthesis in all the templates used. It was also found that a 5-10 times greater concentration is required to attain the same effect in the nuclei as in chromatin. Comparison of the effects of NMU, KNCO and KCl on the template activity of chromatin allows the conclusion that the processes of methylation rather than of carbamoylation of the template are responsible for the decreased RNA synthesis. Sedimentation of the RNA synthesized over the saccharose density gradient demonstrated that the changes in the synthesis are a consequence of the decreased molecular mass of the RNA-transcript, while the number of the RNA molecules synthesized is approximately the same in control and experiment.

[Nature of RNA synthesis on embikhin-damaged templates]. / Kharakteristika sinteza RNK na povrezhdennykh émbikhinom matritsakh.

Embichin, a bifunctional alkylating mutagenic agent, inhibits RNA-synthesizing capacity of DNA and chromatin. The template capacity for decreasing the embichin-injured chromatin is caused by substantial reduction in the number of RNA molecules synthesized by this template. When DNA extracted from embichin-injured chromatin is used as a template, its template restriction is accounted for by an approximately 5-fold decrease in the RNA average molecular weight. The deoxyribonucleoprotein complexes reconstituted from embichin-injured DNA and control chromatic proteins had a lower template capacity compared with that of DNP reconstituted from control DNA. It is concluded that both links between DNA and proteins and DNA injuries are responsible for the inhibition of genome template capacity.

On mechanisms determining the interrelationships between DNA and histone components of chromatin.

The relative affinity of histones for DNA was studied by the analysis of competitive histone binding to DNA in whole histone/DNA mixtures at physiological and low ionic strengths as well as in water. Use of polyphosphate in similar experiments, as a model of DNA deprived of hydrophobic functional groups allowed us to reject the hypothesis that hydrophobic DNA-histone interaction plays a decisive role in the determination of the relative affinity of histones for DNA, because the orders of histone preference for DNA and for polyphosphate were the same. The relative histone affinity for DNA does not depend on the secondary structure of DNA or on the ionic strength of salt solutions, though the differences in the histone affinities for DNA decrease on lowering the salt concentration. The binding orders of the first and the last molecules of histone type to DNA, studied at various DNA/histone ratios in the medium of physiological ionic strength, are the following: H3+H4, H2A+H2B, H1 and H3+H4, H2A, H2B, H1. In water the binding orders of the first and the last histone molecules to DNA are identical: H3+H4, H2A, H2B+H1. It is concluded that the relative histone affinity for DNA in water/salt solutions is determined by non-ionic interactions between histones bound to DNA. The folding of DNA induced by histone-histone interaction seems to lead to the increase in the correlation between amino acid residues in the histone regions bound to DNA and the ionic DNA-histone interaction becoming stronger.

[Formation of DNA--protein crosslinks and their possible elimination in cultures of normal human fibroblasts after exposure to embichin]. / Obrazovanie sshivok DNK-belok i ikh vozmozhnaia éliminatsiia v kul'ture normal'nykh fibroblastov cheloveka posle deistviia émbikhina.

New methods of radiometry and fractionation of cell lysates on hydroxyapatite were applied to determine the crosslinkage between DNA and protein induced by embiquin in cell culture of normal human skin fibroblasts. Such crosslinks were found to be formed; they were eliminated in long-term cultivation of the cells after mutagen treatment.

[Physico-chemical properties of deoxyribonucleoprotamine from sturgeon sperm heads]. / Nekotorye fiziko-khimicheskie svoistva dezoksiribonukleoprotamina iz golovok spermiev osetra

Deoxyribonucleoprotamine (DNPn) from sonicated nuclei of sturgeon sperm heads was studied by means of ring dichroism. A derivative analysis of DNA and DNPn melting curves in 1 mM Tris. HCl pH 8.0 revealed the fraction of protein-free DNA being about 30% and suggested the preferable binding of protamine molecules with AT-rich DNA regions. The latter is also confirmed by the data on ring dichroism of protein-poor soluble DNAPn fraction in 0,14 M NaCl. Ring dichroism of DNA and DNPn in 1 mM Tris coinsides at the wavelength of 310-240 nm at concentrations of 500-50 mkg/ml. Dilution of DNPn to 5 mkg-ml resulted in the decrease of the ellipticity at 275 nm and produced no effect at 260-210 nm. The effect observed is suggested to be due to a partial transition of DNA in DNPn into C-form under the dilution as a result of a higher molecule hydration and a destruction of some hydrogen bonds between guanidine residues of arginine and oxygen of phosphate groups, stabilyzing DNA in the B-form. Ring dichroism spectrum of protamine, calculated by the subtraction of DNA spectrum from DNPn spectrum at the region of 240-210 nm coinsides with that of free protamine and indicates the absence of an ordered structure in protamine molecules in DNPn.

[Effect of embichin (HN2) and its monofunctional analog (HN1) on chromatin and DNA matrix activity in an in vitro RNA-polymerase system]. / Vliianie émbikhina (HN2) i ego monofunktsional'nogo analoga (HN1) na matrichnuiu aktivnost' khromatina i DNK v RNK-polimeraznoi sisteme in vitro

Embichin inhibited the matrix activity of chromatin and DNA in the RNA-polymerase system in vitro much more than its monofunctional analogue. Chromatin possessed a greater sensitivity to the action of embichin in comparison with the deproteinised DNA. However, with the action of a monofunctional embichin analogue there was a greater reduction of the matrix activity of DNA in comparison with chromatin. The depression mechanism of the matrix activity of chromatin with the action of embichin was apparently associated with the capacity of the latter to form the DNA-protein bonds in the chromatin composition.