H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues

Firsanov, Denis; Solovjeva, Ljudmila; Svetlova, Maria

doi:10.1007/s13148-011-0044-4

Cited by 112 publications

(84 citation statements)

References 112 publications

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“…We further evaluated the effects of miR-155 ectopic overexpression on phosphorylated histone family member X (γ-H2AX), which forms nuclear foci at sites of DNA damage, facilitating DNA damage response and repair following IR (38,39).…”

mentioning

confidence: 99%

Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation

Gasparini

Lovat

Fassan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

184

138

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Significance Cell survival after DNA damage relies on DNA repair, the abrogation of which causes genomic instability and development of cancer. DNA double-strand breaks are lesions induced by ionizing radiation (IR) and can be efficiently repaired by DNA homologous recombination, a system that requires RAD51 recombinase (RAD51). Here we show that overexpression of miR-155 in human breast cancer cells reduces the levels of RAD51 and affects the cellular response to IR. High miR-155 levels were associated with lower RAD51 expression and with better overall survival of patients in a large series of triple-negative breast cancers. Testing triple-negative breast cancer patients for miR-155 expression may be a useful prognostic tool to identify who will benefit from an IR-based therapeutic approach.

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mentioning

confidence: 99%

Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation

Gasparini

Lovat

Fassan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

184

138

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“…Phosphorylation of H2AX is a sensitive marker for detection of radiation-induced DSB [162,163]. The number of radiation induced γH2AX foci is closely related to the number of DSB (164,165).…”

Section: Effects Of Carbon Ion Beam On Putative Colon Cancer Stem Celmentioning

confidence: 99%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

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“…(13,14) An early event in DSB response is phosphorylation of the H2A subtype histone H2AX at ser-139 (also known as γH2AX) by the phosphatidylinositol 3-like kinases ATM, ATR and DNA-PK. (15,16) Phosphorylation of H2AX spreads from the site of a DSB into both directions, resulting in initiation and maintenance of DDR. Hence, γH2AX is a recruits several DDR proteins at DSBs and activates DNA repair either by homologous recombination (HR) or non-homologous end joining (NHEJ) (19).…”

Section: Introductionmentioning

confidence: 99%

Overt Increase of Oxidative Stress and DNA Damage in Murine and Human Colitis and Colitis-Associated Neoplasia

Frick

Khare

Paul

et al. 2018

Molecular Cancer Research

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Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC), however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL-10 deficient mice (IL-10 KO). IL-10 KO mice were euthanized after development of colitis and dysplasia. Immunohistochemistry Enhanced DSBs in IL-10 KO organoids were confirmed by comet-assay and increased expression of γH2AX. Human clinical specimens exhibited significantly higher γH2AX and 8-oxoG in IBD, dysplasia and CAC compared to normal mucosa.These data indicate that inflammation-driven colon carcinogenesis in IL-10 KO mice and IBD patients is associated with oxidative DNA damage and overt presence of DSB.on May 9, 2018.

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H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues

Cited by 112 publications

References 112 publications

Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation

Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation

The impact of melatonin and carbon ion irradiation on cancer stem cells

Overt Increase of Oxidative Stress and DNA Damage in Murine and Human Colitis and Colitis-Associated Neoplasia

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