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Biomedical subjects

A P Akif'ev

Publications and source records attributed to A P Akif'ev.

At least 19 recordsLinked to original sources
PubMed2006

[Chromatin diminution at the border of the XX and XXI centuries].

The size of genomes in eukaryotic organisms is one of the greatest mysteries of biology. As known from the middle of the XX century, the level of organization of a particular organism, does not depend on its genome size, i. e. on DNA amount in the nucleus. We believe that an actual function of non-coding DNA stands behind the phenomenon of chromatin diminution, known already for 100 years. Diminution of chromatin normally takes place in cells involved in body building and never occurs in developmental precursors of germ cells. Apparently, the former are cells, in which non-coding DNA is functionally significant. We cloned a fraction of DNA eliminated during chromatin diminution of Cyclops kolensis (Cyclopoida, Crustascea) and sequenced 90 clones totally making 32 kb. Taken together, the provided evidence has demonstrated a high organization ordering of DNA sequences restricted to the germ line. Chromatin diminution never takes place in human cells and in cells of the majority of animals. These cells may isolate non-coding DNA in other ways, making it unreactable for most enzymes and thus functionally cut off. Thus, a certain part of genome with a particular size and structure may serve for genetic isolation of species as shellfish or junk DNA are vital components rather than pieces of garbage.

Animals↗
PubMed2005

[Some conclusions on the role of redundant DNA and the mechanisms of eukaryotic genome evolution inferred from studies of chromatin diminution in Cyclopoida].

The absence of progress in understanding the problem of redundant eukaryotic DNA is stated. This is caused primarily by the attempts to solve this problem either in terms of the traditional approaches (the general phenotypic parameters such as developmental rate, body size, etc. depend on the genome size) or by introducing such vague terms as egoistic, parasitic, or junk DNA. Studying chromatin diminution (CD) in copepods yielded two important conclusions. First, part of the genome of a certain size (94% in Cyclops kolensis first described by the authors) is not needed for somatic functions as it is eliminated during the early (third to seventh) cleavage divisions from the presumptive somatic cells. Second, this DNA is not redundant, let alone selfish or junk, relative to the germline cells. In this sense, it can be regarded as invariant (monomorphic) trait that characterizes the species. Analysis of cloned and sequenced DNA regions eliminated from the somatic cell genome by CD (i.e., confined to the germline), which was first carried out for C. kolensis, showed that the molecular structure of this DNA has at least two features of regular organization: a mosaic structure of repetitive sequences and high (sometimes up to 100%) homology between different repeats and subrepeats. We have suggested that the germline-restricted DNA forms a unique molecular portrait of the species genome, thus acting as a significant factor of genetic isolation. Yet, the phenomenon of CD proper as it occurs in Cyclopoida without disintegration of the chromosome structure) may be regarded as a model of reductional genome evolution, which has repeatedly occurred in the history of eukaryotes.

Animals↗
PubMed2002

[Chromosomal radiosensitivity as associated with chromatin diminution in cyclops (Crustacea, Copepoda)].

Chromosomal radiosensitivity inferred from the yield of chromosome aberrations (CAs) was for the first time studied in Cyclops (Crustacea, Copepoda) before and after chromatin diminution (CD). A comparison was made for C. kolensis, in which CD denudes somatic embryo cells of the greatest (94%) DNA amount known for multicellular organisms, and C. insignis, which lacks CD. The two species have similar genome sizes, 4.6 and 4.3 pg. respectively. Radiosensitivity of C. kolensis chromosomes proved to be extremely high during prediminution cleavage divisions. This was attributed to membrane damage in granules that contain enzymes (topoisomerases) normally involved in cleavage and ligation of chromosomal DNA during CD.

Anaphase↗
PubMed2002

[Chromatin diminution is a key process explaining the eukaryotic genome size paradox and some mechanisms of genetic isolation].

The functions of redundant (junk, selfish, parasitic, etc.) DNA in eukaryotes can be reliably inferred from chromatin diminution (programmed elimination of up to 94% of the genome from somatic germ cells in Ascaris and Cyclops). These functions should be sought in germ cells, where this DNA is preserved during the entire life time of the species. A possible biological role of redundant DNA as a factor disrupting meiotic chromosome synapsis is suggested. At the same time, chromatin diminution itself can act as a mechanism of postzygotic isolation. All stage of the complex diminution mechanism could not be fixed in the genetic program of the species via gradual accumulation of mutations. The "program" of diminution must have appeared at once and in the completed form.

Animals↗
PubMed2001

[Nuclear genetic material as an initial substrate for animal aging].

General properties of aging in animals are considered on the basis of the literature evidence and the results obtained by the authors of this paper. The existence of a specific aging mechanism is inferred. The operation of this mechanism is controlled not only by genes but also by particular noncoding genomic sequences with variable structure. The beginning of senescence in animals is determined by DNA lesions located in neural cells and probably in a minor genomic fraction. The authors refute the narrow concept of aging as a mechanism increasing the probability of death. Mortality as a continuous process occurring with the probability of 100 percent is an integral attribute of living organisms on the Earth.

Aging↗
PubMed1998

[Diminution of chromatin, accompanying reorganization of genomic molecular structure: evolutionary aspects].

Chromatin diminution (CD) accompanied by the reorganization of the molecular genomic structure of macronuclei in ciliates and somatic cells in Cyclops and Ascaris is considered. A conclusion is drawn that the physical elimination of most (sometimes 94-98%) genetic material from somatic nuclei directly indicates that, in these species, eliminated sequences possess neither the coding nor the regulatory functions that are required for differentiation. Apparently, the actual functions of eliminated sequences are associated only with germline chromosomes where these sequences act as a factor of genetic isolation. A CD is supposed to be underlain by the coordinated operation of many genes. Consequently, this phenomenon cannot result from stochastic mutagenesis and the random coincidence of required mutations in several genes. For CD formation, canalized mutagenesis is required, which simultaneously generates a set of genes that code the consecutive stages of CD.

Animals↗
PubMed1995

[The G1-process in human lymphocytes cultured with PHA, and formation of radiation-induced chromosome aberrations].

Experimental evidence for the existence of local spontaneous DNA synthesis in PHA-stimulated human lymphocytes at the G1 phase (G1 process) is presented. This process is associated with the appearance of single-stranded DNA breaks and their subsequent reparation. DNA sequences involved in the G1 process were characterized in terms of their nucleotide composition and association with the nuclear matrix. It was shown that the G1 process occurs in chromosome regions in which radiation-induced exchange-type chromosome aberrations arise. The results of the study are regarded as evidence in favor of a molecular version of the primary contact theory of chromosomal mutagenesis. A possible role of G1 process disturbances in pathogenesis of chromosome instability syndromes in humans is discussed.

Base Composition↗
PubMed1993

[Mutagenesis and genetic homeostasis in higher organisms].

Structural genes and genetic regulatory sites occupy merely a small space in the eukaryotic genome; the remaining space presents various uncoding sequences. Genomic reorganizations, i.e. changes in the mutual arrangements of nucleotide sequences in DNA, appearance of new sequences and disappearance of old ones, have occurred in evolution many times. The genomic reorganizations reflect biological mutagenesis which cannot basically depend on primary DNA damages. Ionizing radiation and traditional chemical mutagens are unable to induce great genomic reorganizations. The cellular genetic apparatus alone plays a key role in maintaining genetic homeostasis and preventing genomic reorganizations. There are some examples of genomic reorganizations in eukaryotes, including those resulting in human hereditary diseases. There are evidence for that chromosomal aberrations occur in the minor site of a genome, which is topologically related to the nuclear matrix.

Animals↗
PubMed1991

[Absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome].

The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment.

Adaptation, Physiological↗
PubMed1988

[Genetic processes and the problem of the target in chromosomal mutagenesis].

Based on analysis of literature data and the data of the authors, it is assumed that there are two main mechanisms of formation of structural chromosome mutations in eukaryotic cells: 1) homologous recombination, resulting in formation of all kinds of chromosome exchanges; 2) the process of telomere formation, resulting in generation of true deletions. Some chromosome breaks registered in the first K mitosis of cells after exposure reflect temporary disturbance of chromatin condensation. These aberrations are able to repair in the next nuclear cycle. The facts are presented that argue in favour of existence of minor fraction of DNA sequences that serve as molecular basis of specific targets of chromosome mutagenesis. These sequences can play essential role in the normal structural and functional organization of nucleus.

Animals↗
PubMed1983

[Radiosensitivity of chromosomes in lymphocytes from Down's syndrome patients].

A study was made of the yield of chromosome aberrations in gamma-irradiated G0 peripheral blood lymphocytes from 6 patients with different forms of Down's syndrome. The doses used were from 0.25 to 3.0 Gy. Seven healthy donors of different age made the control group. There was a significant increase in the yield of chromosome exchanges in lymphocytes from all the patients as compared to control. The spontaneous level of chromosome aberrations and the frequency of radiation-induced fragments did not differ from the control values. The yield of exchanges in diploid and trisomic cells from patients with the mosaic form of Down's syndrome did not change significantly as the time of cultivation was raised. The origin of DNA repair defects leading to the increased chromosome radiosensitivity in Down's syndrome is discussed.

Chromosome Aberrations↗