Synergistic Interaction of Rnf8 and p53 in the Protection against Genomic Instability and Tumorigenesis

Halaby, Marie-Jo; Hakem, Anne; Li, Li; Ghamrasni, Samah El; Somasundaram, Venkatesan; Hande, M. Prakash; Sánchez, Otto; Hakem, Razqallah

doi:10.1371/journal.pgen.1003259

Cited by 19 publications

(19 citation statements)

References 58 publications

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“…Marie-Jo Halaby and colleagues found a synergistic interaction between RNF8 and p53 in the protection against genomic instability and tumorigenesis. 50 In the present study, we further showed that the proliferation of HCT116 p53−/− -shRNF8 cells was faster than that of HCT116 WT -shRNF8 cells. In addition, the level of apoptotic HCT116 p53−/− -shRNF8 cells was significantly lower than that of HCT116 WT -shRNF8 cells (Figure 3).…”

Section: Discussionsupporting

confidence: 68%

RNF8 promotes efficient DSB repair by inhibiting the pro‐apoptotic activity of p53 through regulating the function of Tip60

et al. 2020

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Objectives RING finger protein 8 (RNF8) is an E3 ligase that plays an essential role in DSB repair. p53 is a well‐established tumour suppressor and cellular gatekeeper of genome stability. This study aimed at investigating the functional correlations between RNF8 and p53 in DSB damage repair. Materials and methods In this article, wild‐type, knockout and shRNA‐depleted HCT116 and U2OS cells were stressed, and the roles of RNF8 and p53 were examined. RT‐PCR and Western blot were utilized to investigate the expression of related genes in damaged cells. Cell proliferation, apoptosis and neutral cell comet assays were applied to determine the effects of DSB damage on differently treated cells. DR‐GFP, EJ5‐GFP and LacI‐LacO targeting systems, flow cytometry, mass spectrometry, IP, IF, GST pull‐down assay were used to explore the molecular mechanism of RNF8 and p53 in DSB damage repair. Results We found that RNF8 knockdown increased cellular sensitivity to DSB damage and decreased cell proliferation, which was correlated with high expression of the p53 gene. RNF8 improved the efficiency of DSB repair by inhibiting the pro‐apoptotic function of p53. We also found that RNF8 restrains cell apoptosis by inhibiting over‐activation of ATM and subsequently reducing p53 acetylation at K120 through regulating Tip60. Conclusions Taken together, these findings suggested that RNF8 promotes efficient DSB repair by inhibiting the pro‐apoptotic activity of p53 through regulating the function of Tip60.

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Section: Discussionsupporting

confidence: 68%

RNF8 promotes efficient DSB repair by inhibiting the pro‐apoptotic activity of p53 through regulating the function of Tip60

et al. 2020

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“…DNA strand breaks are considered to be critical primary lesions, which can result in genomic instability and eventually cell death (Halaby et al, 2013). In this study, we observed spinosad-induced DNA double-strand breaks in Sf9 cells (Figure 3(A)).…”

Section: Discussionmentioning

confidence: 54%

Oxidative stress and DNA damage induced by spinosad exposure in Spodoptera frugiperda Sf9 cells

Yang

Gao

et al. 2017

Food and Agricultural Immunology

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Spinosad, a neurotoxic insecticide, is widely used for crop protection. In order to elucidate the effects of spinosad on oxidative stress and genotoxicity in Sf9 cells, the levels of lipid peroxidation, the activity of antioxidative enzymes, and DNA damage were measured. The results showed that spinosad caused a time-dependent increase in the formation of malondialdehyde and decrease in the activity of superoxide dismutase and catalase. Further studies confirmed that spinosad induced 8-oxoguanine accumulation in Sf9 cells, which is accompanied by increased expression of DNA repair enzymes (OGG1 and MTH1). The neutral comet assay revealed that spinosad induced significant timerelated increases of DNA double-strand breaks in Sf9 cells. Our results indicate that spinosad effectively induced oxidative stress and DNA damage in Sf9 cells. ARTICLE HISTORY

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“…Embryonic Stem cells (ES cells) are also suited for metaphase chromosome analysis 9 . If these are not available, fibroblast cells can be used, although a longer treatment with colcemid (e.g., 16 hr with colcemid at a final concentration of 10 ng/ml) is recommended to trap more cells in metaphase before fixation.…”

Section: Discussionmentioning

confidence: 99%

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Misenko

Bunting

2014

JoVE

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Defective DNA repair leads to increased genomic instability, which is the root cause of mutations that lead to tumorigenesis. Analysis of the frequency and type of chromosome aberrations in different cell types allows defects in DNA repair pathways to be elucidated. Understanding mammalian DNA repair biology has been greatly helped by the production of mice with knockouts in specific genes. The goal of this protocol is to quantify genomic instability in mouse B lymphocytes. Labeling of the telomeres using PNA-FISH probes (peptide nucleic acid - fluorescent in situ hybridization) facilitates the rapid analysis of genomic instability in metaphase chromosome spreads. B cells have specific advantages relative to fibroblasts, because they have normal ploidy and a higher mitotic index. Short-term culture of B cells therefore enables precise measurement of genomic instability in a primary cell population which is likely to have fewer secondary genetic mutations than what is typically found in transformed fibroblasts or patient cell lines.

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Synergistic Interaction of Rnf8 and p53 in the Protection against Genomic Instability and Tumorigenesis

Cited by 19 publications

References 58 publications

RNF8 promotes efficient DSB repair by inhibiting the pro‐apoptotic activity of p53 through regulating the function of Tip60

RNF8 promotes efficient DSB repair by inhibiting the pro‐apoptotic activity of p53 through regulating the function of Tip60

Oxidative stress and DNA damage induced by spinosad exposure in Spodoptera frugiperda Sf9 cells

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

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