Assignment of the Equus caballus interleukin 8 gene (IL8) to chromosome 3q14.2-->q14.3 by in situ hybridization.
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Animals↗
Biomedical subjects
S G Nergadze
Publications and source records attributed to S G Nergadze.
Human intrachromosomal telomeric-like repeats: sequence organization and mechanisms of origin.
The intrachromosomal location of (T2AG3)n telomeric sequences has been reported in several species. It was proposed that interstitial telomeres (ITs) originated through telomeric fusion of ancestral chromosomes. However, the data so far obtained derive mainly from cytogenetic observations. Cloning and database searching of human IT sequences allowed us to identify three classes: (i) short ITs, composed of few, essentially exact T2AG3 units; (ii) subtelomeric ITs, composed of larger arrays (several hundred base pairs) including many degenerate units within subtelomeric domains; (iii) fusion ITs, in which two extended stretches of telomeric repeats are oriented head-to-head. The number of short ITs is over 50 and subtelomeric ITs are probably present at all chromosomal ends. Surprisingly, the telomeric sequence in 2q13 remains the only fusion IT so far characterized, and evidence presented here suggests that another member of this class may be present in 1q41. Different molecular mechanisms generated the three classes. In particular, several short ITs interrupt precisely repetitive elements or are flanked by direct repeats of 10-41 bp, and are conserved in gorilla and chimpanzee. These features strongly suggest that telomeric repeats were inserted at intrachromosomal sites through the repair of double-strand breaks that occurred in the germline during evolution.
Animals↗
[Decreased frequency of activation of replicon clusters in Down syndrome lymphocytes].
Human blood lymphocytes from two normal and seven Down syndrome (DS) subjects were examined to determine rates of synthesis of individual replicon and adjacent clusters of replicons, using DNA fiber autoradiography. Lymphocytes in 6 of 7 DS patients were shown to have significantly slower synthesis of simultaneously active adjacent replicon clusters compared to normal controls. Rates of synthesis of individual replicons were the same in lymphocytes from all the subjects investigated. These results demonstrate differences in respect to the structural organization of clusters of replicons between DS and normal lymphocytes. A possible relation of the above phenomenon to the chromosomal radiosensitivity in DS cells is discussed.
Case-Control Studies↗
Decreased number of simultaneously operating adjacent clusters of replicons in some human strains with and without X-irradiation.
Several parameters of DNA replicons and replicon clusters have been examined using DNA fiber autoradiography in normal vs. mutant human cell lines showing increased chromosomal sensitivity to ionizing radiation as well as radioresistant DNA synthesis. Rates of synthesis of individual replicons for unirradiated ataxia telangiectasia (AT) AT5MO, basal cell naevus syndrome (BCNS) BCN1SP and Down's Syndrome LCH944 appeared to be in the range seen with two normal fibroblast lines. With the longer labelling times (60-165 min), the average track lengths were longer in normal fibroblasts than mutant cell; after 5 Gy of radiation, normal and mutant cells had similar track lengths for all labelling times (10-165 min), as well as unchanged rates of replicon synthesis. These observations led to the determination of 'chain length', which measures simultaneously active adjacent replicon clusters. The main finding is that 'chain length' in mutant lines was significantly lower than that in the normal fibroblasts; upon 5 Gy irradiation, the values in normal cells were reduced about two-fold while the values for mutant cells remained about the same as controls. Thus, the experiments suggest that in unirradiated mutant cells DNA replication is delayed in a comparable manner as that induced by ionizing radiation in normal cells. A possible relation of the data to the chromosomal radiosensitivity and radioresistant DNA synthesis in the mutant lines is discussed.
Ataxia Telangiectasia↗
[The mechanism of radioresistant DNA synthesis in ataxia telangiectasia].
Using DNA fiber autoradiography, DNA replication in cells of healthy donors and in those of patients with ataxia telangiectasia (AT) was estimated. A new fact has been demonstrated showing a decreased number of simultaneously operating in tandem groups of replicon clusters in AT cells compared to that in normal cells. The data obtained suggest a reduced frequency of activation in the adjacent replicon clusters in AT cells. It should be noted that the rate of fork movement remained unchanged in AT cells. Besides, the frequency of replication in adjacent replicon clusters remained unaltered after 5 Gy irradiation in AT cells, while the normal cells were radiosensitive to reduction in this replication parameter to the low level seen in both non-irradiated and 5 Gy irradiated AT cells. The relation of the above data to radioresistant DNA synthesis is discussed.
Adult↗
Slower synthesis of individual replicons and adjacent replicon clusters in a radiosensitive xeroderma pigmentosum strain with and without X-irradiation.
Two replication parameters, synthesis of individual replicons and adjacent replicon clusters, were measured using DNA fiber autoradiography in a radiosensitive form of group C xeroderma pigmentosum (XP) XP2SP, in group C XP4SP, in group A Cockayne syndrome (CS) CS1SP and two normal human fibroblast strains. The novel observation here is that in non-irradiated XP2SP cells synthesis of individual replicons was significantly retarded as compared with all other cell lines tested and remained unchanged after 5-Gy X-rays. Also the number of simultaneously operating adjacent replicon clusters was uniquely reduced in only non-irradiated XP2SP cells and remained unaltered after 5-Gy irradiation. While the normal, XP4SP and CS1SP cells are radiosensitive to reduction in this replication parameter to a low level seen in both non-irradiated and 5-Gy irradiated XP2SP cells. Thus, non-irradiated XP2SP cells mimic irradiated normal, XP4SP and CS1SP cells. A possible relation of the above abnormalities in individual replicons and adjacent replicon clusters to a high incidence of spontaneous sister-chromatid exchanges and X-irradiation-induced chromosomal aberrations in XP2SP cells is discussed.
Cells, Cultured↗
[The retardation of DNA synthesis in adjacent replicon clusters in the lymphocytes of patients with Down's syndrome as a model of premature aging].
In peripheral blood lymphocytes taken from 7 patients with Down syndrome (DS) and 2 normal donors, using DNA fiber autoradiography, we estimated the rate of DNA-chain growth, which depends oil the number of simultaneously replicating adjacent replicon clusters, but not on the rate of fork movement. No difference was found in the rate of fork movement in these cells. 6 of 7 DS patients showed a significant reduction in the rate of DNA-chain growth as compared to that in normal control. Thus, a new molecular defect in DS lymphocytes has ben first revealed. Besides, new arguments have been provided in favour of genetic heterogeneity of this genetic disorder belonging to premature ageing diseases. Relation of molecular DNA replication defects with ageing is discussed.
Aging↗
[The relation of the characteristics of DNA replication to cell sensitivity to ionizing radiation in xeroderma pigmentosum in form II (XP2CP)].
Using DNA fiber autoradiography, DNA replication in cultured fibroblasts, derived from normal donors, and from XPII patient with increased sensitivity to ionizing radiation was estimated. Here evidence is provided on the fact that the fork movement, significantly decreased in XPII cells before irradiation, remains the same after exposure to X-rays. The density of replicon clusters simultaneously operating in tandem groups, which is initially much less in XPII cells compared to normal cells, also remains unchanged after exposure to X-rays (5 Gy), since the inhibition of DNA replication occurs to individual replicons only. Our data suggest that the inhibition of DNA replication in normal cells throughout the whole cluster, that drastically reduces the rate of DNA-chain growth, may provide an additional time to restore damaged chromosomes, i. e. it is part of the cellular defence mechanism. It seems likely that XPII cells are deficient in such a defence mechanism.
Autoradiography↗
[DNA replication in intact and X-ray-irradiated cells in the Cockayne syndrome].
Using DNA fiber autoradiography, an estimation was made of DNA replication in normal fibroblasts and in those derived from a patient with Cockayne syndrome. The rate of replication fork movement as well as the rate of DNA chain growth, dependent on the frequency of initiation sites in the adjacent clusters of replicons, did not differ in Cockayne syndrome cells, compared to cells of normal donors, either before or after exposure to ionizing radiation.
Autoradiography↗
[The interrelation between changes in the structural organization of replicon clusters, a retarded fork displacement rate and the high level of spontaneous SCEs in form II of xeroderma pigmentosum].
A cytogenetic observation, that the sister chromatid exchanges (SCE) occur 3 times more frequently in a special form of xeroderma pigmentosum--XPII than in the norm, prompted a study of DNA replication in this rare disease. Using DNA fiber autoradiography, the rate of fork movement and the frequency of initiation in the adjacent clusters of replicons were estimated. The rate of fork movement was significantly slower than that in classical XP and in normal cells. Here evidence was provided on another defect in DNA replication in XPII that involves a significantly decreased number of simultaneously operating adjacent clusters of replicons, which results in a decreased rate of DNA chain-growth. According to the Painter replication model for SCE, the exchanges arise due to double-strand DNA breaks occurring on the border between two adjacent clusters, respectively, completely and partially replicated. A retarded fork-displacement rate together with a decreased rate of DNA-chain growth may cause this situation to persist longer than in the norm. Thus, our data provide a further support of the replication model for SCE. A similar combination of cytogenetic and molecular defects has been obtained earlier in the Bloom syndrome cells.
Autoradiography↗
[The effect of staphylococcal alpha-toxin on DNA replication in human cells].
The influence of Staphylococcus alpha-toxin has been investigated on the duration of S-phase of lymphocyte mitotic cycle and on DNA replication in human fibroblasts in vitro. The duration of the S-phase of lymphocytes was measured by counting labeled metaphases and by making replication curves. Alpha-toxin in a dose of 3 micrograms/ml enhances the onset of S-phase, which is inhibited at a dose of 33 micrograms/ml of alpha-toxin. The action of alpha-toxin resulted in a decreased rate of replication fork and in a progressive activation of replicon groups. This effect was most prominent at 33 micrograms/ml of alpha-toxin. The data obtained allow to suggest that immunodeficiency of the second order, so characteristic of the staphylococcal sepsis, may be due, in many respects, to suppression of DNA replication.
Autoradiography↗
[The action of ionizing radiation on DNA replication in the cells of a healthy human subject and of a patient with Down's syndrome].
Using DNA fiber autoradiography we have revealed a new defect earlier unknown in Down's syndrome but analogous to that earlier shown by the authors in AT and basal cell nevus. This syndrome involves a significantly decreased number of simultaneously operating groups of replicons compared to that in normal cells., the rate of fork movement and the fusion of neighbouring units in the group being unchanged. Ionizing radiation (5 Gy) does not change the rate of DNA chain growth in the cells derived from the affected individuals, however, it significantly reduces this parameter in normal cells due to inhibition of replicon initiation in the whole clusters. Thus, radioresistant DNA synthesis in chromosomal instability syndromes may be explained by some defect in DNA replication in unirradiated cells analogous to that in irradiated normal cells.
Autoradiography↗
[Disruption of DNA replication in non-irradiated cells in basal cell nevus syndrome and the effect of ionizing radiation].
Analysis of DNA fiber autoradiograms from basal cell nevus syndrome (BCNS) skin fibroblasts has revealed for the first time a new defect in DNA replication earlier unknown in other chromosomal instability syndromes, that involves a significantly decreased rate of DNA-chain growth in unirradiated cells. Here we present evidence that the defect may be due to a marked reduction in number of simultaneously operating groups of replicons compared to that in normal cells, the rate of fork movement and the fusion of neighbouring units in the group remaining unchanged. Radioresistant DNA synthesis was observed in the BCNS cells. The exposure of cells derived from normal donor to gamma-rays at a dose of 5 Gy reduces the number of simultaneously operating groups of replicons to the level occurring in unirradiated BCNS cells, the rate of folk movement being unchanged in both cell types. However, the incidence of fusion between neighbouring units within the group is lower in the cells exposed to gamma-rays, due perhaps to a radiation-induced lesion in the group. Thus, ionizing radiation reduces the rate of DNA synthesis to the same level, however from different initial levels. Our data suggest that the phenomenon of radioresistant DNA synthesis may be explained by the presence of the initial defect in DNA replication in BCNS or any other chromosomal instability disorders.
Adult↗
[Changes in the cytogenetic indices in the bone marrow cells of white rats undergoing mechanical trauma of various degrees of severity].
The influence of traumatic shock on some cytogenetic indices in bone marrow cells was investigated in white mongrel rats. The traumatic shock was caused by the Noble-Collip method. Comparative analyses of cytogenetic indices during trauma of different intensity show that the most acute changes involve the percentage of aberrant metaphases, and of average number of chromosome breaks per cell. Dynamics of changes of cytogenetic indices after a heavy trauma show that the traumatic shock may exert a cytogenetic effect maintaining for 18 hours. The results obtained and the analysis of literary data enables us to suggest that the speed of development of changes, and restoration of cytogenetic indices under various forms of trauma is quite different and may serve another confirmation of the hypothesis above the possibility of increasing the process of mutagenesis at the expense of the violation of homeostasis.
Animals↗