In studies on the mechanism of DNA damage response where ionizing radiation is used as the DNA damaging agent, cells are often exposed to ionizing radiation on melting ice (corresponding to 0.8 °C). The purpose of this procedure is to inhibit cellular processes i.e. DNA repair. Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage, but its mechanisms of action are poorly understood. The aim of the study was to analyze the effect of hypothermia at the level of formation and decay of NBS1, γH2AX, and 53BP1 foci, micronuclei, survival, cell cycle progression and oxidative stress in U2OS cells. The results show that hypothermia alone induced oxidative stress and foci. When applied in combination with radiation but only during the exposure time, it potentiated the formation of γH2AX and 53BP1 but not of NBS1 foci. When applied during irradiation and subsequent repair time, 53BP1 and NBS1 foci formed and decayed, but the levels were markedly lower than when repair was carried out at 37 °C. The frequency of micronuclei was elevated in cells irradiated at 0.8 °C, but only when analysed 20 h after irradiation which is likely due to a reduced G cell cycle block. Hypothermia reduced cell survival, both with and without radiation exposure. The temperature effect should be considered when cooling cells on melting ice to inhibit DNA repair in the induction of DNA damage.
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http://dx.doi.org/10.1038/s41598-022-09829-y | DOI Listing |
PLoS Biol
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
The organization of the human genome in space and time is critical for transcriptional regulation and cell fate determination. However, robust methods for tracking genome organization or genomic interactions over time in living cells are lacking. Here, we developed a multicolor DNA labeling system, ParSite, to simultaneously track triple genomic loci in the U2OS cells.
View Article and Find Full Text PDFMol Med
January 2025
Research Institute, National Cancer Center, Goyang-Si, Gyeonggi-Do, 10408, Republic of Korea.
Background: Double-strand breaks (DSBs) are primarily repaired through non-homologous end joining (NHEJ) and homologous recombination (HR). Given that DSBs are highly cytotoxic, PARP inhibitors (PARPi), a prominent class of anticancer drugs, are designed to target tumors with HR deficiency (HRD), such as those harboring BRCA mutations. However, many tumor cells acquire resistance to PARPi, often by restoring HR in HRD cells through the inactivation of NHEJ.
View Article and Find Full Text PDFNat Cancer
January 2025
Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Tumors lacking the BRCA1 and BRCA2 (BRCA) hereditary breast cancer genes display heightened sensitivity to anti-cancer treatments, such as inhibitors of poly (ADP-ribose) polymerase 1 (PARP1). However, when resistance develops, treatments are lacking. Using CRISPR technology, we discovered that enhancing homologous recombination through increased DNA end resection in BRCA1-deficient cells by loss of the 53BP1-Shieldin complex-which is associated with resistance to PARP inhibitors-also heightens sensitivity to DNA nicks.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Life Sciences, Hebei University, Baoding 071002, China.
Bovine herpesvirus 1 (BoHV-1) productive infection induces the generation of DNA double-strand breaks (DSBs), which may consequently lead to cell apoptosis. In response to DSBs, the DNA damage repair-related protein 53BP1 is recruited to the sites of DSBs, leading to the formation of 53BP1foci, which are crucial for the repair of damaged DNA and maintaining genomic integrity by repairing DSBs. In this study, we discovered that HMGA1 may play a significant role in counteracting virus infection-induced DNA damage, as the siRNA-mediated knockdown of HMGA1 protein expression or inhibition of HMGA1 activity by the chemical inhibitor Netropsin uniformly exacerbates the DNA damage induced by BoHV-1 productive infection.
View Article and Find Full Text PDFInt J Radiat Biol
January 2025
N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Background: Enumeration of residual DNA repair foci 24 hours or more after exposure to ionizing radiation (IR) is often used to assess the efficiency of DNA double-strand break repair. However, the relationship between the number of residual foci in irradiated cells and the radiation dose is still poorly understood. The aim of this work was to investigate the dose responses for residual DNA repair foci in normal human fibroblasts after X-ray exposure in the absorbed dose range from 0.
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