Copy Number Variation of Human Satellite III (1q12) With Aging

Abstract

Introduction: Human satellite DNA is organized in long arrays in peri/centromeric heterochromatin. There is little information about satellite copy number variants (CNVs) in aging and replicative cell senescence (RS). Materials and Methods: Biotinylated pUC1.77 probe was used for the satellite III (f-SatIII) quantitation in leukocyte DNA by the non-radioactive quantitative hybridization for 557 subjects between 2 and 91 years old. The effect of RS and genotoxic stress (GS, 4 or 6 µM of K 2 CrO 4 ) on the f-SatIII CNV was studied on the cultured human skin fibroblast (HSF) lines of five subjects. Results: f-SatIII in leukocyte and HSFs varies between 5.7 and 40 pg/ng of DNA. During RS, the f-SatIII content in HSFs increased. During GS, HSFs may increase or decrease f-SatIII content. Cells with low f-SatIII content have the greatest proliferative potential. F-SatIII CNVs in different individuals belonging to the different generations depend on year of their birth. Children (born in 2005–2015 years) differed significantly from the other age groups by low content and low coefficient of variation of f-SatIII. In the individuals born in 1912–1925 and living in unfavorable social conditions (FWW, the Revolution and the Russian Civil War, SWW), there is a significant disproportion in the content of f-SatIII. The coefficient of variation reaches the maximum values than in individuals born in the period from 1926 to 1975. In the group of people born in 1990–2000 (Chernobyl disaster, the collapse of the Soviet Union, and a sharp decline in the population living standard), again, there is a significant disproportion of individuals in the content of f-SatIII. A similar disproportion was observed in the analysis of a group of individuals born in 1926–1975 who in their youth worked for a long time in high-radioactive environment. Conclusion: In generations that were born and who lived in childhood in a period of severe social perturbations or in conditions of environmental pollution, we found a significant increase in leukocyte DNA f-SatIII variability. It is hypothesized that the change of the f-SatIII content in the blood cells reflects the body response to stress of different nature and intensity.

1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia

“…In that case, the ribosomal repeat content in the cells does not change. A similar response we observed in a cultured skin fibroblasts population exposed to the different genotoxic agent Cr(VI) concentrations (Ershova et al, 2019c).…”

“…We found that ∼40% of the irradiated people have significantly reduced f-SatIII content compared to non-irradiated people of the same age. We also observed that the f-SatIII content decreased in the cultured HSFs under oxidizing agent Cr(VI) (Ershova et al, 2019c). All these facts suggest that there is a common mechanism leading to the f-SatIII repeat content decrease in the healthy cells under oxidative stress induced by environmental factors and in the cells of SZ patients during the disease exacerbation.…”

“…This process leads to the f-SatIII content increase in the cell's DNA (Bersani et al, 2015), and these cells replenish the cells fraction with a large f-SatIII repeat size. Cells with a high f-SatIII content accumulate in the population during natural and replicative aging (Ershova et al, 2019c) and under low IR doses ( Figure 5D). Such cells are not able to proliferate and die under more intense exposure being not capable to an AR.…”

“…The AR increases the cells' resistance to stress (Sokolov and Neumann, 2015;Sisakht et al, 2020). Thus, cells with a low f-SatIII content have a large proliferative potential and genotoxic stress resistance (Ershova et al, 2019c).…”

“…The rising roles of satellite tandem repeats in genome organization and disease development were suggested ( Iafrate et al, 2004 ; Sebat et al, 2004 ; Dumbovic et al, 2017 ). In our previous studies, we described the CNVs of two tandem repeats in human blood leukocytes: ribosomal repeat ( Chestkov et al, 2018a ; Malinovskaya et al, 2018 ) and satellite III fragment (f-SatIII), localized in the largest heterochromatin region 1q12 of the first chromosome ( Ershova et al, 2019a , c ).…”