scholarly journals BMS-345541 Sensitizes MCF-7 Breast Cancer Cells to Ionizing Radiation by Selective Inhibition of Homologous Recombinational Repair of DNA Double-Strand Breaks

2012 ◽  
Vol 179 (2) ◽  
pp. 160 ◽  
Author(s):  
Lixian Wu ◽  
Lijian Shao ◽  
Manna Li ◽  
Junying Zheng ◽  
Junru Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Selective Inhibition ◽  
Double Strand Breaks ◽  
Recombinational Repair ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Recombinational Repair ◽  
Mcf 7

scholarly journals IKKβ Regulates the Repair of DNA Double-Strand Breaks Induced by Ionizing Radiation in MCF-7 Breast Cancer Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18447 ◽  
Author(s):  
Lixian Wu ◽  
Lijian Shao ◽  
Ningfei An ◽  
Junru Wang ◽  
Senthil Pazhanisamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Mcf 7

The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells

2012 ◽  
Vol 30 (5) ◽  
pp. 1917-1925 ◽  
Author(s):  
Hong Jue Lee ◽  
Petra Burger ◽  
Marianne Vogel ◽  
Klaus Friese ◽  
Ansgar Brüning
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

scholarly journals Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4421
Author(s):  
Agnieszka Korga-Plewko ◽  
Monika Michalczyk ◽  
Grzegorz Adamczuk ◽  
Ewelina Humeniuk ◽  
Marta Ostrowska-Lesko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Oxidative Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Interaction Mechanism ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Mcf 7

A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.

scholarly journals RecO impedes RecG-SSB binding to impair the strand annealing recombination pathway in E.coli

2019 ◽  
Author(s):  
Xuefeng Pan ◽  
Li Yang ◽  
Nan Jiang ◽  
Xifang Chen ◽  
Bo Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Dna Replication ◽  
Replication Fork ◽  
Double Strand Breaks ◽  
Recombinational Repair ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Recombinational Repair ◽  
Differential Binding

AbstractFaithful duplication of genomic DNA relies not only on the fidelity of DNA replication itself, but also on fully functional DNA repair and homologous recombination machinery. We report a molecular mechanism responsible for deciding homologous recombinational repair pathways during replication dictated by binding of RecO and RecG to SSB in E.coli. Using a RecG-yfp fusion protein, we found that RecG-yfp foci appeared only in the ΔrecG, ΔrecO and ΔrecA, ΔrecO double mutants. Surprisingly, foci were not observed in wild-type ΔrecG, or double mutants where recG and either recF or, separately recR were deleted. In addition, formation of RecG-yfp foci in the ΔrecO::kanR required wildtype ssb, as ssb-113 could not substitute. This suggests that RecG and RecO binding to SSB is competitive. We also found that the UV resistance of recO alone mutant increased to certain extent by supplementing RecG. In an ssb-113 mutant, RecO and RecG worked following a different pattern. Both RecO and RecG were able to participate in repairing UV damages when grown at permissive temperature, while they could also be involved in making DNA double strand breaks when grown at nonpermissive temperature. So, our results suggested that differential binding of RecG and RecO to SSB in a DNA replication fork in Escherichia coli.may be involved in determining whether the SDSA or DSBR pathway of homologous recombinational repair is used.Author summarySingle strand DNA binding proteins (SSB) stabilize DNA holoenzyme and prevent single strand DNA from folding into non-B DNA structures in a DNA replication fork. It has also been revealed that SSB can also act as a platform for some proteins working in DNA repair and recombination to access DNA molecules when DNA replication fork needs to be reestablished. In Escherichia coli, several proteins working primarily in DNA repair and recombination were found to participate in DNA replication fork resumption by physically interacting with SSB, including RecO and RecG etc. However the hierarchy of these proteins interacting with SSB in Escherichia coli has not been well defined. In this study, we demonstrated a differential binding of RecO and RecG to SSB in DNA replication was used to establish a RecO-dependent pathway of replication fork repair by abolishing a RecG-dependent replication fork repair. We also show that, RecG and RecO could randomly participate in DNA replication repair in the absence of a functional SSB, which may be responsible for the generation of DNA double strand breaks in an ssb-113 mutant in Escherichia coli.

scholarly journals Histone H2AX Promotes Metastatic Progression by Preserving Glycolysis via Hexokinase-2

2021 ◽  
Author(s):  
Yue Liu ◽  
Haojian Li ◽  
Crystal Wilson ◽  
Hui Jen Bai ◽  
Myriem Boufraqech ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Metastatic Breast ◽  
Genomic Stability ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Energetic Metabolism ◽  
Strand Breaks ◽  
Histone H2ax

Abstract Genomic stability is essential for organismal development, cellular homeostasis, and survival. The DNA double-strand breaks are particularly deleterious, creating an environment prone to cellular transformation and oncogenic activation. The histone variant H2AX is an essential component of the nucleosome responsible for initiating the early steps of the DNA repair process. H2AX maintains genomic stability by initiating a signaling cascade that collectively functions to promote DNA double-strand breaks repair. Recent advances have linked genomic stability to energetic metabolism, and alterations in metabolism were found to interfere with genome maintenance. Utilizing genome-wide transcripts profiling to identify differentially-expressed genes involved in energetic metabolism, we compared control and H2AX-deficient metastatic breast cancer cell lines, and found that H2AX loss leads to the repression of key genes regulating glycolysis, with a prominent effect on hexokinase-2 (HK2). These observations are substantiated by evidence that H2AX loss compromises glycolysis, effect which was reversed by ectopic expression of HK2. Utilizing models of experimental metastasis, we found that H2AX silencing halts progression of metastatic breast cancer cells MDA-MB-231. Most interestingly, ectopic expression of HK2 in H2AX-deficient cells restores their metastatic potential. Using multiple publicly available datasets, we found a significantly strong positive correlation between H2AX expression levels in patients with invasive breast cancer, and levels of glycolysis genes, particularly HK2. These observations are consistent with the evidence that high H2AX expression is associated with shorther distant metastasis-free survival. Our findings reveal a role for histone H2AX in controlling the metastatic ability of breast cancer cells via maintenance of HK2-driven glycolysis.

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