4. Laboratory of Genome Structure.
(1) Staff:
- Grigory M. Dymshits, Prof., Dr.Sci., Head of the Laboratory
- Vyacheslav A. Adarichev, Ph.D.
- Anna E. Dikalova, Ph.D.
- Natalia A. Dudareva, Ph.D.
- Sergei M. Kalachikov, Ph.D.
- Valentina I. Rykova, Ph.D.
- Inna E. Vlassova, Ph.D.
- Ivan B. Khvorostov
- Angelika A. Krivenko
- Alexander V. Popovsky
- Wjatschesslaw A. Wlassoff
(2) Subject of Research:
- Structure-function organization of eukaryotic genome.
- Nonradioactive detection of different sequences in the human and animal genomes.
- Synthesis of the nucleoside 5'-triphosphate derivatives bearing the photoreactive groups and fluorescent labels.
- Studies of substrate and template specificity of different RNA and DNA polymerases from various domains of life.
- Study of nuclear proteoglicans participation in the regulation of gene expression.
- Investigation of the molecular-genetic mechanisms of human hypertension using the rat strain with inherited stress-induced arterial hypertension.
- Plant mitochondrial genome structure. Expression of mitochondrial genes in fertile and
sterile sugar beet cytoplasms.
(3) General Results 1993-1995:
New original methods of the synthesis of nucleoside
5'-triphosphate derivatives bearing the residues of various
fluorescent dyes and photoreagents have been fulfilled and the
compounds obtained have been studied as substrates for different DNA
and RNA polymerases.
A model for the DNA polymerase translocation along the DNA has
been proposed. According to the model, the movement of the enzyme is a
result of transition of the enzyme-bound DNA from A- to B-form which
is accompanied by the lenghtening of DNA within the binding channel.
An original method of preparation of nonradioactively labelled
DNA and RNA probes for molecular hybridization has been suggested. The
method is based on incorporation of amino groups into polynucleotides
by alkylation and transamination of nucleic base followed by
attachment of different labels to these amino groups. The level of
labelling of such probes by biotin and fluorochroms which gives
maximal sensitivity during dot-, blot- and in situ hybridization has
been determined.
The use of high sensitive biotinilated DNA probes allows to map
the human horionic somatomammotropin gene to the 17q22 region.
The new method of the DNA photoimmobilization onto the different
solid supports which allows to increase the hybridization sensitivity
have been developed.
The test-systems for nonradioactive DNA diagnostics of bovine
leukemia provirus, Malaria in human blood, and mycoplasmic
contamination of cell cultures have been developed.
It has been shown that nuclear proteoglicans are very
conservative in mammalian cells. The oligo RNAs from the nuclear
proteoglican fraction are able to suppress a transcriptional process in
cell culture.
The ISIAH (inherited stress-induced arterial hypertension) rat
strain has been characterized by DNA fingerprinting method, and very
high genetic homogeneity has been shown.
It has been carried out the mapping of point mutations in leader
sequence of the hsp70 gene of various rat strains with hypertensive and
normotensive status. The ISIAH rat strain has been shown to carry the
point mutation in the leader sequence at a distance of 35 bp from the
start of the transcription origin in the recognition site of
restrictase BamHI.
The molecular-genetic differences between the fertile and sterile
types of cytoplasm in sugar beet have been revealed. The mechanism of
spontaneous conversion of normal cytoplasm to sterile one has been
suggested.
It has been demonstrated that the rearrangements in mitochondrial
DNA appeared during in vitro cultivation of plant cells, part of them
has been inherited by regenerated plants. The data have been obtained
providing the hypothesis that the higher generation of free oxygen
radicals under stress conditions of culturing may be a cause of
somaclonal variation.
(4) Publications:
- Dikalova A.E., Dudareva N.A., Kubalakova M., Salganik R.I.
(1993). Rearrangements in the sugar beet mitochondrial DNA induced by
cell suspension, callus cultures and regeneration. Theor.Appl.Genet.
86:699-704.
- Popov A.N., Adarichev V.A., Kalachikov S.M., Mishina E.S.,
Dymshits G.M. (1993). Detection of bovine leukemia provirus by
polimerase chain reaction followed by nonradioactive blot
hybridization. Problems of virology 38:113-116. (Rus.)
- Vlasova I.E., Vlasov V.V. (1993). Molecular evolution: design
of nucleic acids possessing catalytic properties and capable of
specific complex formation. Molecular Biology 27:1-5.
- Adarichev V.A., Dymshits G.M., Mishina E.S., Salganik R.I.,
Sokhanenkova T.L. Nonradioactive hybridization test onto the
Plasmodium falciparum invasion. Biopolymers and cells 9:19-23.
(Rus.)
- Wlassoff W.A., Kalachikov S.M, Dymshits G.M. (1994). Synthesis
of fluorescent labelled uridine 5'-triphosphate derivatives for
preparation of nonradioactive RNA probes. Bioorg. Chem. 20:676-681.
(Rus.)
- Kalachikov S.M., Kel' A.E., Dymshits G.M., Ishov A.M.,
Borkhsenius S.N. (1994). Cloning of universal hybridization probes for
testing mycoplasmal contamination in cell cultures. Molecular Biology
28:298-302.
- Vlassova I.E., Nechaeva M.V., Vlassov V.V. (1994). Systems of
delivering nucleic acids to cells of mammals. Achievments of modern
biology 114:715-726. (Rus.)
- Zamaraev K.I., Salganik R.I., Romannikov V.N., Wlassoff
W.A., Khramtsov V.V. (1995). The modelling of prebiotic synthesis of
oligopeptides in the presence of zeolites and kaolin. Rep. of Russ.
Acad. Sci. 340:779- 782. (Rus.)
- Wlassoff W.A., Dobrikov M.I., Safronov I.V., Dudko R.Y.,
Bogachev V.S., Kandaurova V.V., Shishkin G.V., Dymshits G.M., Lavrik
O.I. (1995). Synthesis and characterization of (d)NTP derivatives
substituted with residues of different photoreagents. Bioconjugate
Chemistry 6:352- 360.
- Adarichev V.A., Vorob'eva N.V., Grafodatsky A.S., Dymshits
G.M., Sablina O.V. (1995). DNA modification with
4-aminohydroxybutylamine to obtain highly sensitive hybridization
probes. Location of human chorionic somatomammotropin gene. Molecular
Biology 29:307-311.
- . Dikalova A.E., Veprev S.G., Maletsky S.I., Salganik R.I.
(1995). Polymorphism of mitochondrial genome structure in plants of
Beta vulgaris L. with normal cytoplasms. Rep. of Russ. Acad. Sci.
(Rus., in press)
(5) Participation in State and International Programs:
- New Trends in Genetics
- Human genome
- RFBR
(6) Subjects of Scientific Collaboration:
- Structure-function organization of eukaryotic genome.
- Nonradioactive detection of different sequences in the human and animal genomes.
- Studies of substrate and template specificity of different RNA and DNA polymerases from various domains of life.
- Investigation of the molecular-genetic mechanisms of human
hypertension using the rat strain with inherited stress-induced
arterial hypertension. Analysis of linkage of stress-responsiveness
and high arterial blood pressure with the set of molecular-genetic
markers.
- Plant mitochondrial genome structure. Expression of mitochondrial
genes in fertile and sterile sugar beet cytoplasms.