Residual Foci of DNA Damage Response Proteins in Relation to Cellular Senescence and Autophagy in X-Ray Irradiated Fibroblasts

Abstract

DNA repair (DNA damage) foci observed 24 h and later after irradiation are called “residual” in the literature. They are believed to be the repair sites for complex, potentially lethal DNA double strand breaks. However, the features of their post-radiation dose-dependent quantitative changes and their role in the processes of cell death and senescence are still insufficiently studied. For the first time in one work, a simultaneous study of the association of changes in the number of residual foci of key DNA damage response (DDR) proteins (γH2AX, pATM, 53BP1, p-p53), the proportion of caspase-3 positive, LC-3 II autophagic and SA-β-gal senescent cells was carried out 24–72 h after fibroblast irradiation with X-rays at doses of 1–10 Gy. It was shown that with an increase in time after irradiation from 24 h to 72 h, the number of residual foci and the proportion of caspase-3 positive cells decrease, while the proportion of senescent cells, on the contrary, increases. The highest number of autophagic cells was noted 48 h after irradiation. In general, the results obtained provide important information for understanding the dynamics of the development of a dose-dependent cellular response in populations of irradiated fibroblasts.

ABI3BP promotes renal aging through Klotho-mediated ferroptosis

“…Osipov et al [ 16 ], established that X-ray irradiation accelerates mouse aging. Therefore, in our study, mice were randomly divided into a control group and a radiation-induced aging group.…”

Dose-Dependent Shift in Relative Contribution of Homologous Recombination to DNA Repair after Low-LET Ionizing Radiation Exposure: Empirical Evidence and Numerical Simulation

“…where the [ssDNA •RPA] complex is the same as that shown in Equation (12). The junction between Rad52 heptamer rings and each ssDNA termini that allowed the formation of a flapped structure is represented as follows:…”

“…One of the initial events involved in the complex process of DNA repair from DSBs is the phosphorylation of the core histone H2AX by kinases of the PIKK families (phosphatidylinositol 3 kinase-related kinases) ATM, ATR and DNA-PKcs in the flanking regions of DSBs of chromatin [ 9 ]. Dynamic microstructures containing thousands of copies of the phosphorylated histone H2AX (γ-H2AX), which are called “foci” in the literature, are easily visualized using immunocytochemical staining [ 10 , 11 , 12 ]. The analysis of γH2AX foci provides information regarding the number of DNA repair sites derived from DSBs, their distribution over the nuclear volume, and their impact on the kinetics of repair.…”

Post-Radiation Changes in The Number of Phosphorylated H2ax and Atm Protein Foci in Low Dose X-Ray Irradiated Human Mesenchymal Stem Cells

“…ДР составляют относительно небольшую часть радиационно-индуцированных повреждений ДНК, но именно они являются основным триггером, определяющим дальнейшую судьбу клетки. Клеточный ответ на воздействие ионизирующего излучения напрямую зависит от числа накопленных ДР ДНК и может включать такие процессы, как остановка клеточного цикла, активация процессов репарации ДНК и запуск программ клеточной гибели или старения [7][8][9].…”