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DNA damage repair

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https://www.readbyqxmd.com/read/28821159/inhibition-of-dna-pk-enhances-chemosensitivity-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-to-doxorubicin
#1
Fatemeh Alikarami, Majid Safa, Mohammad Faranoush, Parisa Hayat, Ahmad Kazemi
DNA damage repair pathways greatly affect the response to genotoxic drugs in cancer cells, so inhibition of such pathways could be a potentially useful strategy to enhance chemosensitivity. DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DNA double-strand breaks (DSBs) that are probably one of the most detrimental types of DNA damage. It has been shown that DNA-PK is highly expressed in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Less well appreciated was the effect of DNA-PK inhibition on sensitivity of BCP-ALL cells to DNA-damaging agents...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28820495/human-papillomavirus-and-the-dna-damage-response-exploiting-host-repair-pathways-for-viral-replication
#2
REVIEW
Chelsey C Spriggs, Laimonis A Laimins
High-risk human papillomaviruses (HPVs) are the causative agents of cervical and other genital cancers. In addition, HPV infections are associated with the development of many oropharyngeal cancers. HPVs activate and repress a number of host cellular pathways to promote their viral life cycles, including those of the DNA damage response. High-risk HPVs activate the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) DNA damage repair pathways, which are essential for viral replication (particularly differentiation-dependent genome amplification)...
August 18, 2017: Viruses
https://www.readbyqxmd.com/read/28820390/small-molecule-inhibitors-of-dna-pk-for-tumor-sensitization-to-anticancer-therapy
#3
M Pospisilova, M Seifrtova, M Rezacova
The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820355/alpha-particles-and-x-rays-interact-in-inducing-dna-damage-in-u2os-cells
#4
Alice Sollazzo, Beata Brzozowska, Lei Cheng, Lovisa Lundholm, Siamak Haghdoost, Harry Scherthan, Andrzej Wojcik
Survivors of the atomic bombings of Hiroshima and Nagasaki are monitored for health effects within the Life Span Study (LSS). The LSS results represent the most important source of data about cancer effects from ionizing radiation exposure, which forms the foundation for the radiation protection system. One uncertainty connected to deriving universal risk factors from these results is related to the problem of mixed radiation qualities. The A-bomb explosions generated a mixed beam of the sparsely ionizing gamma radiation and densely ionizing neutrons...
August 18, 2017: Radiation Research
https://www.readbyqxmd.com/read/28819638/connecting-androgen-receptor-signaling-and-the-dna-damage-response-development-of-new-therapies-for-advanced-prostate-cancer
#5
Timothy C Thompson, Likun Li
Androgen receptor-mediated cell signaling involves complex molecular pathways that are interconnected with DNA damage response, including replication stress-driven DNA repair. Understanding the relationships between androgen receptor signaling and DNA damage response at the molecular level will likely lead to novel and effective combination therapy for advanced prostate cancer.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28819025/mre11-promotes-tumorigenesis-by-facilitating-resistance-to-oncogene-induced-replication-stress
#6
Elizabeth Spehalski, Kayla M Capper, Cheryl J Smith, Mary J Morgan, Maria Dinkelmann, Jeffrey Buis, JoAnn M Sekiguchi, David O Ferguson
Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double strand breaks where it functions in repair and triggers cell cycle checkpoints via activation of the ataxia-telangiectasia mutated (ATM) kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Both forms of MRN deficiency led to hallmarks of cancer, including oncogenic translocations involving c-Myc and the immunoglobulin locus...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818866/systematic-identification-of-determinants-for-single-strand-annealing-mediated-deletion-formation-in-saccharomyces-cerevisiae
#7
Maia Segura-Wang, Megumi Onishi-Seebacher, Adrian M Stütz, Balca R Mardin, Jan O Korbel
To ensure genomic integrity, living organisms have evolved diverse molecular processes for sensing and repairing damaged DNA. If improperly repaired, DNA damage can give rise to different types of mutations, an important class of which are the genomic structural variants (SVs). In spite of their importance for phenotypic variation and genome evolution, potential contributors to SV formation in Saccharomyces cerevisiae (budding yeast), a highly tractable model organism, are not fully recognized. Here we developed and applied a genome-wide assay to identify yeast gene knock-out mutants associated with de novo deletion formation, in particular single strand annealing (SSA) -mediated deletion formation in a systematic manner...
August 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28818740/assessment-of-genotoxicity-of-four-volatile-pollutants-from-cigarette-smoke-based-on-the-in-vitro-%C3%AE-h2ax-assay-using-high-content-screening
#8
Sen Zhang, Huan Chen, An Wang, Yong Liu, Hongwei Hou, Qingyuan Hu
To evaluate the genotoxic effects of formaldehyde, acetaldehyde, acrolein and benzene on A549 cells, the in vitro γH2AX assay was used in combination with high content screening (HCS) technology. All aldehydes showed a significant genotoxicity in a dose/time-dependent effect on the induction of γH2AX. Benzene failed to show a significant genotoxicity based on the γH2AX assay. However, hydroquinone (one of metabolites of benzene) showed a significant genotoxicity in vitro. Based on the dose-response of γH2AX and Hill model, the ability to induce DNA double-strand break can be evaluated as acrolein>formaldehyde>acetaldehyde>benzene...
July 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28817778/the-oxidation-state-of-4fe4s-clusters-modulates-the-dna-binding-affinity-of-dna-repair-proteins
#9
Edmund C M Tse, Theodore J Zwang, Jacqueline K Barton
A central question important to understanding DNA repair is how certain proteins are able to search for, detect, and fix DNA damage on a biologically relevant timescale. A feature of many base excision repair proteins is that they contain [4Fe4S] clusters that may aid their search for lesions. In this report, we establish the importance of the oxidation state of the redox-active [4Fe4S] cluster in the DNA damage detection process. We utilize DNA-modified electrodes to generate repair proteins with [4Fe4S] clusters in the 2+ and 3+ states by bulk electrolysis under an O2-free atmosphere...
August 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28815640/in-vitro-genotoxicity-of-airborne-ni-np-in-air-liquid-interface
#10
Siiri Latvala, Daniel Vare, Hanna L Karlsson, Karine Elihn
Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively...
August 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#11
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#12
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814116/the-dark-side-of-the-ring-role-of-the-dna-sliding-surface-of-pcna
#13
Matteo De March, Alfredo De Biasio
The proliferating cell nuclear antigen (PCNA) sliding clamp lies at the heart of the accurate duplication of eukaryotic genomes. While the outer surface of the PCNA ring interacts with polymerases and other factors, the role of the inner wall facing the DNA is elusive. Recent evidence shows that conserved basic residues in the PCNA central channel create a specific surface that recognizes the DNA backbone and enables the clamp to slide by rotationally tracking the DNA helix. The sliding surface can be modulated (i) through lysine acetylation, which triggers PCNA degradation during nucleotide excision repair (NER) and stimulates repair by homologous recombination (HR) or (ii) through binding of the protein factor p15(PAF), which turns off DNA lesion bypass...
August 17, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28813668/subnuclear-relocalization-of-structure-specific-endonucleases-in-response-to-dna-damage
#14
Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28812526/parvovirus-infection-is-associated-with-myocarditis-and-myocardial-fibrosis-in-young-dogs
#15
Jordan Ford, Laura McEndaffer, Randall Renshaw, Alex Molesan, Kathleen Kelly
Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28810535/curcumin-enhances-the-radiosensitivity-of-renal-cancer-cells-by-suppressing-nf-%C3%AE%C2%BAb-signaling-pathway
#16
Gang Li, Ziming Wang, Tie Chong, Jie Yang, Hongliang Li, Haiwen Chen
The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810532/plga-ctab-curcumin-nanoparticles-fabrication-characterization-and-molecular-basis-of-anticancer-activity-in-triple-negative-breast-cancer-cell-lines-mda-mb-231-cells
#17
Ramovatar Meena, Sumit Kumar, Raj Kumar, Usha Singh Gaharwar, Paulraj Rajamani
Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells)...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28808232/analysis-of-the-atr-chk1-and-atm-chk2-pathways-in-male-breast-cancer-revealed-the-prognostic-significance-of-atr-expression
#18
Anna Di Benedetto, Cristiana Ercolani, Marcella Mottolese, Francesca Sperati, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Matthew P Humphries, Luigi Di Lauro, Maddalena Barba, Ilio Vitale, Gennaro Ciliberto, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
The ATR-Chk1 and ATM-Chk2 pathways are central in DNA damage repair (DDR) and their over-activation may confer aggressive molecular features, being an adaptive response to endogenous DNA damage and oncogene-induced replication stress. Herein we investigated the ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC). The expression of DDR kinases (pATR, pATM, pChk1, pChk2, and pWee1) and DNA damage markers (pRPA32 and γ-H2AX) was evaluated by immunohistochemistry in 289 MBC samples to assess their association...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808021/kinetic-and-high-throughput-profiling-of-epigenetic-interactions-by-3d-carbene-chip-based-surface-plasmon-resonance-imaging-technology
#19
Shuai Zhao, Mo Yang, Wenfei Zhou, Baichao Zhang, Zhiqiang Cheng, Jiaxin Huang, Min Zhang, Zhiyou Wang, Rui Wang, Zhonglei Chen, Jinsong Zhu, Haitao Li
Chemical modifications on histones and DNA/RNA constitute a fundamental mechanism for epigenetic regulation. These modifications often function as docking marks to recruit or stabilize cognate "reader" proteins. So far, a platform for quantitative and high-throughput profiling of the epigenetic interactome is urgently needed but still lacking. Here, we report a 3D-carbene chip-based surface plasmon resonance imaging (SPRi) technology for this purpose. The 3D-carbene chip is suitable for immobilizing versatile biomolecules (e...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28806503/identification-of-the-dimer-exchange-interface-of-the-bacterial-dna-damage-response-protein-umud
#20
David A Murison, Rebecca C Timson, Bilyana Koleva, Michael Ordazzo, Penny J Beuning
The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both non-mutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product, UmuD', together with UmuC, form the Y-family polymerase DNA Pol V (UmuD'2C) capable of performing TLS...
August 14, 2017: Biochemistry
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