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Article
Open AccessFisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells
Triple-negative breast cancer (TNBC) is associated with aggressiveness and a poor prognosis. Besides surgery, radiotherapy serves as the major treatment modality for TNBC. However, response to radiotherapy is ...
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Article
Open AccessSCFSKP2 regulates APC/CCDH1-mediated degradation of CTIP to adjust DNA-end resection in G2-phase
The cell cycle-dependent engagement of DNA-end resection at DSBs is regulated by phosphorylation of CTIP by CDKs, the central regulators of cell cycle transitions. Cell cycle transitions are also intimately re...
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Article
Open AccessDNA-PKcs and ATM epistatically suppress DNA end resection and hyperactivation of ATR-dependent G2-checkpoint in S-phase irradiated cells
We previously reported that cells exposed to low doses of ionizing radiation (IR) in the G2-phase of the cell cycle activate a checkpoint that is epistatically regulated by ATM and ATR operating as an integrated ...
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Article
Open AccessRewiring E2F1 with classical NHEJ via APLF suppression promotes bladder cancer invasiveness
Bladder cancer progression has been associated with dysfunctional repair of double-strand breaks (DSB), a deleterious type of DNA lesions that fuel genomic instability. Accurate DSB repair relies on two distin...
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Article
Open AccessRadiation-dose-dependent functional synergisms between ATM, ATR and DNA-PKcs in checkpoint control and resection in G2-phase
Using data generated with cells exposed to ionizing-radiation (IR) in G2-phase of the cell cycle, we describe dose-dependent interactions between ATM, ATR and DNA-PKcs revealing unknown mechanistic underpinnings ...
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Article
Open AccessThe presumed MTH1-inhibitor TH588 sensitizes colorectal carcinoma cells to ionizing radiation in hypoxia
The nudix family member enzyme MutT homologue-1 (MTH1) hydrolyses the oxidized nucleotides 8-oxo-dGTP and 2-hydroxy-dATP and thus prevents the incorporation of damaged nucleotides into nuclear and mitochondria...
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Chapter
The Biological Foundations of Risks from Ionizing Radiation Exposures: How an Understanding of Associated Effects Will Help Their Quantification and Mitigation
Ionizing radiation induces a severe form of DNA damage through clustering of ionizations: the DNA double-strand break (DSB).
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Chapter
Processing-Challenges Generated by Clusters of DNA Double-Strand Breaks Underpin Increased Effectiveness of High-LET Radiation and Chromothripsis
Whereas most endogenous and exogenous DNA damaging agents typically generate lesions that are relatively isolated and can be repaired easily, ionizing radiation (IR) also induces clustered lesions causing DNA ...
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Article
Wenn Stränge reißen – Wege der DNA-Doppelstrangbruch-Reparatur
The most severe DNA-damage is the double-strand break (DSB) which, if not processed correctly, can lead to cell death or cancer. Cells have evolved two fundamentally different DSB repair mechanisms. Homologous...
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Article
Deregulated BCL-2 family proteins impact on repair of DNA double-strand breaks and are targets to overcome radioresistance in lung cancer
DNA damage-induced cell death is a major effector mechanism of radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is frequently observed in lung cancers. Against this background, we stud...
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Article
Open AccessReduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
In cells exposed to low linear energy transfer (LET) ionizing-radiation (IR),double-strand-breaks (DSBs) form within clustered-damage-sites (CDSs) fromlesions disrupting the DNA sugar-phosphate backbone. It is...
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Article
Open AccessProcessing of DNA double strand breaks by alternative non-homologous end-joining in hyperacetylated chromatin
Mammalian cells employ at least two subpathways of non-homologous end-joining for the repair of ionizing radiation induced DNA double strand breaks: The canonical DNA-PK-dependent form of non-homologous end-jo...
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Protocol
In Vitro Rejoining of Double Strand Breaks in Genomic DNA
Recent genetic and biochemical studies have provided important insights into the mechanism of nonhomologous end joining (NHEJ) pathways in higher eukaryotes, and have facilitated the functional characterizatio...
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Protocol
Analysis of Inhibition of DNA Replication in Irradiated Cells Using the SV40 Based In Vitro Assay of DNA Replication
The deleterious effects of DNA damage on DNA replication have been demonstrated in many model systems and the mechanisms of the resulting inhibition have been a research focus for at least 40 years. Moreover, ...
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Protocol
Application of Alkaline Sucrose Gradient Centrifugation in the Analysis of DNA Replication After DNA Damage
Sucrose density gradient ultracentrifugation is a powerful technique for fractionating macromolecules like DNA, RNA, and proteins. For this purpose, a sample containing a mixture of different size macromolecul...
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Chapter
Backup Pathways of Nonhomologous End Joining May Have a Dominant Role in the Formation of Chromosome Aberrations
Chromosome aberrations are large-scale chromatin rearrangements produced in cells after exposure to ionizing radiation and other DNA-damaging agents. They have been directly implicated in cell killing, mutatio...
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Protocol
Plasmid-Based Assays for DNA End-Joining In Vitro
Double-strand breaks (DSBs) disrupt DNA integrity and cause genomic instability and cancer, mutations, or cell death. Among the pathways utilized by cells of higher eukaryotes to repair this lesion, nonhomolog...
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Protocol
In Vitro Rejoining of Double-Strand Breaks in Genomic DNA
Recent genetic and biochemical studies have provided important insights into the mechanism of nonhomologous end-joining (NHEJ) in higher eukaryotes, and have helped to characterize several components including...
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Protocol
Analysis of Inhibition of DNA Replication in Irradiated Cells Using the SV40-Based In Vitro Assay of DNA Replication
The mechanisms of inhibition of DNA replication after DNA damage through the activation of the S-phase checkpoint have been the focus of several investigations over the last 40 yr. Recent studies have identifi...
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Article
Interferon alpha 2a downregulates VEGF expression through PI3 kinase and MAP kinase signaling pathways
An earlier report demonstrated that interferon alpha (IFN-α) inhibited tumor growth and recurrence in an MHCC97 xenograft model in nude mice by suppressing tumor angiogenesis rather than by inhibiting tumor c...
