PubMed Health⌕ Search

Biomedical subjects

A M Olovnikov

Publications and source records attributed to A M Olovnikov.

30 records · Page 2Linked to original sources
PubMedDate not supplied

Telomeres, telomerase, and aging: origin of the theory.

In 1971 I published a theory in which I first formulated the DNA end replication problem and explained how it could be solved. The solution to this problem also provided an explanation for the Hayflick Limit, which underpins the discovery of in vitro and in vivo cell senescence. I proposed that the length of telomeric DNA, located at the ends of chromosomes consists of repeated sequences, which play a buffer role and should diminish in dividing normal somatic cells at each cell doubling. I also proposed that the loss of sequences containing important information that could occur after buffer loss could cause the onset of cellular senescence. I also suggested that for germline cells and for the cells of vegetatively propagated organisms and immortal cell populations like most cancer cell lines, an enzyme might be activated that would prevent the diminution of DNA termini at each cell division, thus protecting the information containing part of the genome. In the last few years, most of my suggestions have been authenticated by laboratory evidence. the DNA sequences that shorten in dividing normal cells are telomeres and the enzyme that maintains telomere length constant in immortal cell populations is telomerase.

Aging↗
PubMedDate not supplied

[Intranuclear ion fountains as regulators of genome work: fountain hypothesis of dominance and some epigenetic effects].

It is hypothesized that gene function is modulated through the action of the ion channels of the internal nuclear membrane, and that this underlies the phenomenon of dominance and some epigenetic effects. The topographic specificity essential to gene regulation by injecting portions of ions--ion fountains--is ensured by special fountain RNAs (fRNAs), which operate as double-stranded molecules, and fions, the fRNA-binding sites on the DNA. Every specific fion.fRNA complex then binds with the protein of an ion channel in the inner nuclear membrane, whereby this channel briefly opens to dispense, e.g., Ca2+, Zn2+, or K+ from the perinuclear cistern into the nucleus, as defined by the specificity of fRNA, fion, and the channel chosen by them. Fions may be situated both in introns of genes and at their flanks, even quite far from the target gene. Allelic fions, that is, fions located in homologous sites of homologous chromosomes but differing in the capacity of binding different fRNAs, will unequally influence the ionic surroundings of their structural genes. Ion channels can provide the dominant allele with an ionic atmosphere dissimilar from that of the recessive allele. Distinctions in the nature, number, and location of fions may be the main reason why the dominant and recessive alleles of a structural gene differ in activity even though their other properties are identical. Unequal changes occurring in the vicinity of the alleles may involve chromatin configuration, transcriptional activity of the gene, mRNA processing and lifespan. Isolation of structural genes in a chromosome by long intergene spacers, and large distances between chromosomes in the nucleus prevent undesirable interference of ion fountains. Fions may be key components of many enhancers and silencers. The performance of fions may be affected by pairing of homologous nucleotide sequences of chromosomes, which generates a number of epigenetic effects, such as transvection and gene position effect. Excessive approach of a structural gene to inadequate ion fountains may cause unscheduled chromatin compaction and gene suppression.

Cations↗
PubMedDate not supplied

[The role of incomplete terminal repair of chromosomal DNA in the aging of neurons and postmitotic organisms].

Incomplete repair of the DNA double helix terminus is an independent mechanism of the telomeric DNA shortening in non-dividing cells. This effect of incomplete terminal DNA repair may initiate aging of postmitotic neuroendocrine cells or even whole postmitotic organisms, if loss of the buffer telomeric DNA (due to incomplete terminal repair) is followed by the loss of significant information in the nucleotide sequences. We also consider a possibility of local aging of a cell group, e.g., in the locomotor system where extreme physical load favors accumulation of nuclear factors inducing accelerated shortening of telomeric DNA.

Animals↗