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    ZEB1 confers chemotherapeutic resistance to breast cancer by activating ATM.
    Cell Death Dis 2018 Jan 19;9(2):57. Epub 2018 Jan 19.
    Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.
    Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms. Read More

    1H, 15N, and 13C chemical shift assignments of the micelle immersed FAT C-terminal (FATC) domains of the human protein kinases ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) fused to the B1 domain of streptococcal protein G (GB1).
    Biomol NMR Assign 2018 Jan 18. Epub 2018 Jan 18.
    Department of Chemistry, Biomolecular NMR Spectroscopy, Technische Universität München, Lichtenbergstr. 4, 85747, Garching, Germany.
    FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent NMR- and CD-monitored interaction studies indicated that the FATC domains of all PIKKs can interact with membrane mimetics albeit with different preferences for membrane properties such as surface charge and curvature. Read More

    MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.
    Oncotarget 2017 Dec 6;8(68):112980-112991. Epub 2017 Dec 6.
    Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo. Read More

    Loss of NEIL3 DNA glycosylase markedly increases replication associated double strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells.
    Oncotarget 2017 Dec 4;8(68):112942-112958. Epub 2017 Dec 4.
    Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX, United States.
    DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Read More

    Radiosensitization of the PI3K inhibitor HS-173 through reduction of DNA damage repair in pancreatic cancer.
    Oncotarget 2017 Dec 1;8(68):112893-112906. Epub 2017 Dec 1.
    Department of Drug Development, College of Medicine, Inha University, Sinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.
    Activation of PI3K/AKT pathway occurs frequently in tumors and is correlated with radioresistance. The PI3K/AKT pathway can be an important target for improvement of radiotherapy. Although adding of chemotherapy to radiation therapy regimen enhances survival in patients with locally advanced pancreatic cancer, more effective therapies for increasing radiosensitivity are urgently needed. Read More

    Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment.
    Curr Med Chem 2018 Jan 16. Epub 2018 Jan 16.
    Department of Clinical Chemistry and Biochemistry, Military-Medical Faculty, Medical University of Lodz, Lodz. Poland.
    Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death. Read More

    Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.
    Oncol Lett 2017 Dec 13;14(6):7825-7828. Epub 2017 Oct 13.
    Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
    The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0. Read More

    Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response.
    Retrovirology 2018 Jan 16;15(1). Epub 2018 Jan 16.
    Department of Intractable Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
    Background: Viral protein R (Vpr) is an accessory protein of HIV-1, which is potentially involved in the infection of macrophages and the induction of the ataxia-telangiectasia and Rad3-related protein (ATR)-mediated DNA damage response (DDR). It was recently proposed that the SLX4 complex of structure-specific endonuclease is involved in Vpr-induced DDR, which implies that aberrant DNA structures are responsible for this phenomenon. However, the mechanism by which Vpr alters the DNA structures remains unclear. Read More

    A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.
    PLoS One 2018 16;13(1):e0190821. Epub 2018 Jan 16.
    Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI.
    Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. Read More

    Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model.
    IET Syst Biol 2018 Feb;12(1):26-38
    Department of Electrical-Electronics Engineering, Yaşar University, Bornova, İzmir 35100, Turkey.
    This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. Read More

    Whole-genome sequencing reveals principles of brain retrotransposition in neurodevelopmental disorders.
    Cell Res 2018 Jan 12. Epub 2018 Jan 12.
    Cancer Research Center and the Wohl Institute of Translational Medicine, the Chaim Sheba Medical Center, Tel Hashomer, Israel.
    Neural progenitor cells undergo somatic retrotransposition events, mainly involving L1 elements, which can be potentially deleterious. Here, we analyze the whole genomes of 20 brain samples and 80 non-brain samples, and characterized the retrotransposition landscape of patients affected by a variety of neurodevelopmental disorders including Rett syndrome, tuberous sclerosis, ataxia-telangiectasia and autism. We report that the number of retrotranspositions in brain tissues is higher than that observed in non-brain samples and even higher in pathologic vs normal brains. Read More

    ATM directs DNA damage responses and proteostasis via genetically separable pathways.
    Sci Signal 2018 Jan 9;11(512). Epub 2018 Jan 9.
    Howard Hughes Medical Institute, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. Read More

    Regulation of mitophagy by the ubiquitin pathway in neurodegenerative diseases.
    Exp Biol Med (Maywood) 2018 Jan 1:1535370217752351. Epub 2018 Jan 1.
    Department of Biochemistry and Molecular Biology, LSUHSC-School of Medicine, New Orleans, LA 70112, USA.
    Mitophagy is a cellular process by which dysfunctional mitochondria are degraded via autophagy. Increasing empirical evidence proposes that this mitochondrial quality-control mechanism is defective in neurons of patients with various neurodegenerative diseases such as Ataxia Telangiectasia, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Accumulation of defective mitochondria and the production of reactive oxygen species due to defective mitophagy have been identified as causes underlying neurodegenerative disease pathogenesis. Read More

    DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions.
    Proc Natl Acad Sci U S A 2018 Jan 8. Epub 2018 Jan 8.
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115;
    Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical nonhomologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining that is more biased to use longer junctional microhomologies (MHs). Read More

    Pancreatic cancer screening in high-risk individuals with germline genetic mutations.
    Gastrointest Endosc 2018 Jan 5. Epub 2018 Jan 5.
    Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America. Electronic address:
    Background And Aims: Pancreas cancer (PC) is a deadly disease, which is most commonly diagnosed at an incurable stage. Different high-risk genetic variants and cancer syndromes increase the lifetime risk of developing PC. This study aims to assess the yield of initial PC screening in patients with high-risk germline mutations. Read More

    ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells.
    J Gastric Cancer 2017 Dec 15;17(4):295-305. Epub 2017 Nov 15.
    Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin, China.
    Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined.

    Materials And Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Read More

    T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib).
    Blood Adv 2017 Dec 18;1(27):2724-2728. Epub 2017 Dec 18.
    Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.
    A 19-year-old ataxia-telangiectasia patient with T-cell prolymphocytic leukemia harbored 2 JAK3-activating hotspot mutations.The patient suffered toxicities with chemotherapy, but demonstrated a clinical response to novel use of a JAK3 inhibitor (tofacitinib). Read More

    Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage.
    Nucleic Acids Res 2017 Dec 27. Epub 2017 Dec 27.
    Department of Oncology, CRUK & MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
    ATM (ataxia-telangiectasia mutated) is a central molecule for DNA quality control. Its activation by DNA damage promotes cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, persistent DNA damage has been implicated in ATM-dependent cell death via apoptosis; however, the mechanisms underlying this process remain elusive. Read More

    Long-term nutritional and gastrointestinal aspects in patients with ataxia telangiectasia.
    Nutrition 2018 Feb 24;46:48-52. Epub 2017 Aug 24.
    Pediatric Gastroenterology and Nutrition Unit, The Edmond and Lily Safra Children's Faculty of Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Sackler Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address:
    Objective: Ataxia telangiectasia (A-T) is a rare genetic disease involving multiple organs, but, to our knowledge, data on long-term gastrointestinal and nutritional involvement are scarce. The aim of this study was to longitudinally review the nutritional and gastrointestinal aspects of A-T.

    Methods: This was a retrospective chart review of patients followed from 1986 to 2015 at one center. Read More

    Telangiectasias in Ataxia Telangiectasia: Clinical significance, role of ATM deficiency and potential pathophysiological mechanisms.
    Eur J Med Genet 2017 Dec 26. Epub 2017 Dec 26.
    Department of Pediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
    Ataxia Telangiectasia (AT) is named after the two key clinical features that characterize its classical phenotype, namely a progressive cerebellar gait disorder (ataxia) and vascular anomalies (telangiectasias) visible in the conjunctivae and skin. AT is an autosomal recessively inherited disorder, caused by mutations in the ATM gene that encodes the ATM protein. While the ataxia is subject of many publications, the telangiectasias are under emphasised. Read More

    Ganoderma lucidum polysaccharide enhances radiosensitivity of hepatocellular carcinoma cell line HepG2 through Akt signaling pathway.
    Exp Ther Med 2017 Dec 18;14(6):5903-5907. Epub 2017 Oct 18.
    Department of Pharmacy, The First Affiliated Hospital of The General Hospital of The People's Liberation Army of China, Beijing 100048, P.R. China.
    Ganoderma lucidum polysaccharide (GLP) is a well-known traditional Chinese medicine, known for its anti-cancer and immunomodulatory properties. The present study aims to investigate whether GLP has a therapeutic effect on hepatocellular carcinoma (HCC) cells exposed to radiation. Immunofluorescence was used to detect the nuclei, the protein expression was measured by western blot analysis and flow cytometry was used to detect the rate of cell apoptosis. Read More

    Hair Follicle Stem Cell Faith Is Dependent on Chromatin Remodeling Capacity Following Low-Dose Radiation.
    Stem Cells 2017 Dec 28. Epub 2017 Dec 28.
    Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany.
    The main function of the skin, to protect against the environment, is supported by the activity of different stem cell populations. The main focus of this study was elucidating the coping mechanisms of stem cells against the stimulation of constant exposure to genotoxic stresses, both endogenous and exogenous, to ensure long-term function. Investigation of various mouse strains, differing in their DNA repair capacity, enables us to clarify fractionated low-dose irradiation (LDR)-induced consequences for different stem cell populations of the murine hair follicle (HF) in their physiological stem cell niche. Read More

    Challenges in implementing model-based phase I designs in a grant-funded clinical trials unit.
    Trials 2017 Dec 28;18(1):620. Epub 2017 Dec 28.
    CRUK MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
    Background: For a clinical trials unit to run its first model-based, phase I trial, the statistician, chief investigator, and trial manager must all acquire a new set of skills. These trials also require a different approach to funding and data collection.

    Challenges And Discussion: From the statisticians' viewpoint, we highlight what is needed to move from running rule-based, early-phase trials to running a model-based phase I study as we experienced it in our trials unit located in the United Kingdom. Read More

    7-hydroxy-staurosporine, UCN-01, induces DNA damage response and autophagy in human osteosarcoma U2-OS cells.
    J Cell Biochem 2017 Dec 26. Epub 2017 Dec 26.
    Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
    Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. Read More

    ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.
    Proc Natl Acad Sci U S A 2018 Jan 26;115(2):E292-E301. Epub 2017 Dec 26.
    Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;
    ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. Read More

    Point mutation in p14ARF -specific exon 1β of CDKN2A causing familial melanoma and astrocytoma.
    Br J Dermatol 2017 Dec 26. Epub 2017 Dec 26.
    Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT) at Translational Research Institute, 37 Kent Street, Woolloongabba, 4102, QLD.
    Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for >85% of mutation-positive families (1). CDKN2A encodes two, non-homologous proteins, p16 and p14ARF , with individually unique first exons (1α and 1β, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript (1). Read More

    Cryo-EM structure of human ATR-ATRIP complex.
    Cell Res 2017 Dec 22. Epub 2017 Dec 22.
    Fudan University Shanghai Cancer Center, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
    ATR (ataxia telangiectasia-mutated and Rad3-related) protein kinase and ATRIP (ATR-interacting protein) form a complex and play a critical role in response to replication stress and DNA damage. Here, we determined the cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex at 4.7 Å resolution and built an atomic model of the C-terminal catalytic core of ATR (residues 1 521-2 644) at 3. Read More

    Non-BRCA1/2 Breast Cancer Susceptibility Genes: A New Frontier with Clinical Consequences for Plastic Surgeons.
    Plast Reconstr Surg Glob Open 2017 Nov 20;5(11):e1564. Epub 2017 Nov 20.
    Hansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, New York, N.Y.; and Department of Surgery, NYU Langone Medical Center, New York, N.Y.
    Twenty percent of breast cancer cases may be related to a genetic mutation conferring an increased risk of malignancy. The most common and prominent breast cancer susceptibility genes are BRCA1 and BRCA2, found in nearly 40% of such cases. However, continued interest and investigation of cancer genetics has led to the identification of a myriad of different breast cancer susceptibility genes. Read More

    The fate of murine double minute X (MdmX) is dictated by distinct signaling pathways through murine double minute 2 (Mdm2).
    Oncotarget 2017 Nov 6;8(61):104455-104466. Epub 2017 Nov 6.
    Department of Pediatrics, Herman B Wells Center for Pediatrics Research, Indianapolis, Indiana, 46202, United States of America.
    Mouse double minute 2 (Mdm2) and MdmX dimerize in response to low levels of genotoxic stress to function in a ubiquitinating complex, which signals for destabilization of p53. Under growth conditions, Mdm2 functions as a neddylating ligase, but the importance and extent of MdmX involvement in this process are largely unknown. Here we show that when Mdm2 functions as a neddylating enzyme, MdmX is stabilized. Read More

    Molecular chemotherapeutic potential of butein: A concise review.
    Food Chem Toxicol 2017 Dec 16;112:1-10. Epub 2017 Dec 16.
    Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea. Electronic address:
    Butein is a biologically active flavonoid isolated from the bark of Rhus verniciflua Stokes, which is known to have therapeutic potential against various cancers. Notably, butein inhibits cancer cell growth by inducing G2/M phase arrest and apoptosis. Butein-induced G2/M phase arrest is associated with increased phosphorylation of ataxia telangiectasia mutated (ATM) and Chk1/2, and consequently, with reduced cdc25C levels. Read More

    How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery.
    Viruses 2017 Dec 19;9(12). Epub 2017 Dec 19.
    Clinical Pathology and Microbiology Unit, San Gallicano Dermatology Institute, IRCCS, IFO, Via Elio Chianesi 53, 00144 Rome, Italy.
    The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. Read More

    Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair.
    Nucleic Acids Res 2017 Dec 14. Epub 2017 Dec 14.
    Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
    The DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and a crucial player in the DSB response. Read More

    Two girl patients with medulloblastoma. Case reports.
    Rom J Morphol Embryol 2017 ;58(3):1103-1108
    Department of Pediatrics, University of Medicine and Pharmacy of Craiova, Romania;
    In childhood, the most common type of brain tumors is medulloblastoma, a highly malignant primary brain tumor that is found in the cerebellum or posterior fossa. The tumor mass increases and generates obstructive hydrocephalus. Risk factors (that might be involved in some cases) include the genetic syndrome such as type 1 neurofibromatosis, exposure to ionizing radiation and Epstein-Barr virus. Read More

    More than ataxia - Movement disorders in ataxia-telangiectasia.
    Parkinsonism Relat Disord 2018 Jan 12;46:3-8. Epub 2017 Dec 12.
    Movement Disorders Centre, Toronto Western Hospital, Toronto University, Toronto, ON, Canada. Electronic address:
    Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative disease caused by mutations in the ATM gene with progressive neurological dysfunction, multisystem abnormalities and cancer predisposition. Classically, AT is associated with cerebellar ataxia, oculocutaneous telangiectasia and oculomotor apraxia. The aim of this review is to describe the movement disorders observed in patients with AT. Read More

    DNA damage response-initiated cytokine secretion in bone marrow stromal cells promotes chemoresistance of myeloma cells.
    Leuk Lymphoma 2017 Dec 18:1-7. Epub 2017 Dec 18.
    a Department of Hematology , Xijing Hospital, Fourth Military Medical University , Xi'an , Shaanxi , China.
    Acquisition of chemoresistance accounts for a major cause of chemotherapy failure for multiple myeloma (MM). Bone marrow stromal cells (BMSCs) are considered to play a pivotal role in modulating drug resistance of MM cells. However, the underlying mechanism whereby BMSCs, particularly damaged stromal cells, affects chemoresistance has not been identified yet. Read More

    Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis.
    BMC Pulm Med 2017 Dec 15;17(1):205. Epub 2017 Dec 15.
    Department of Respiratory Medicine and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guoxuexiang 37, Chengdu, 610041, China.
    Background: Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Read More

    DNA damage causes rapid accumulation of phosphoinositides for ATR signaling.
    Nat Commun 2017 Dec 14;8(1):2118. Epub 2017 Dec 14.
    Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.
    Phosphoinositide lipids (PPIs) are enriched in the nucleus and are accumulated at DNA damage sites. Here, we investigate roles of nuclear PPIs in DNA damage response by sequestering specific PPIs with the expression of nuclear-targeted PH domains, which inhibits recruitment of Ataxia telangiectasia and Rad3-related protein (ATR) and reduces activation of Chk1. PPI-binding domains rapidly (< 1 s) accumulate at damage sites with local enrichment of PPIs. Read More

    Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response.
    Nutr Res 2017 Nov 18;47:63-71. Epub 2017 Sep 18.
    School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China. Electronic address:
    Punicalagin (PUN), a component derived from pomegranate, is well known for its anticancer activity. Our previous work revealed that PUN induces autophagic cell death in papillary thyroid carcinoma cells. We hypothesized that PUN triggers DNA damage associated with cell death because DNA damage was reported as an inducer of autophagy. Read More

    Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer.
    Front Oncol 2017 29;7:291. Epub 2017 Nov 29.
    Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, United States.
    The ataxia-telangiectasia mutated (ATM) protein kinase has been extensively studied for its role in the DNA damage response and its association with the disease ataxia telangiectasia. There is increasing evidence that ATM also plays an important role in other cellular processes, including carbon metabolism. Carbon metabolism is highly dysregulated in cancer due to the increased need for cellular biomass. Read More

    E2F/DP Prevents Cell-Cycle Progression in Endocycling Fat Body Cells by Suppressing dATM Expression.
    Dev Cell 2017 Dec 7;43(6):689-703.e5. Epub 2017 Dec 7.
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149 13(th) Street, Charlestown, MA 02129, USA. Electronic address:
    To understand the consequences of the complete elimination of E2F regulation, we profiled the proteome of Drosophila dDP mutants that lack functional E2F/DP complexes. The results uncovered changes in the larval fat body, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue. Read More

    EBV-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma.
    J Pathol 2017 Dec 12. Epub 2017 Dec 12.
    Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong.
    Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. Read More

    Helichrysetin Induces DNA Damage that Triggers JNK-Mediated Apoptosis in Ca Ski Cells.
    Pharmacogn Mag 2017 Oct-Dec;13(52):607-612. Epub 2017 Nov 13.
    Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
    Background: Cervical cancer has become one of the most common cancers in women and currently available treatment options for cervical cancer are very limited. Naturally occurring chalcones and its derivatives have been studied extensively as a potential anticancer agent in different types of cancer and helichrysetin is naturally occurring chalcone that possess potent antiproliferative activity toward human cancer cells.

    Materials And Methods: Inhibitory activity of helichrysetin was evaluated at different concentrations. Read More

    Ataxia Telangiectasia and Cancer Predisposition: Challenges in Management.
    J Pediatr Hematol Oncol 2017 Dec 1. Epub 2017 Dec 1.
    Department of Pediatrics, Division of Pediatric Hematology Oncology, Vanderbilt University Medial Center, Nashville, TN.
    Immune dysregulation and predisposition to malignancies are critical comorbidities in children affected with ataxia telangiectasia. In addition, these children exhibit increased toxicity to conventional cancer therapy and dose reductions have been proposed to prevent life threatening adverse effects. These modifications to the treatment regimen may result in suboptimal outcomes for these patients. Read More

    3.9 Å structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP.
    Science 2017 Dec;358(6367):1206-1209
    Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
    The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master regulator of DNA damage response and replication stress in humans, but the mechanism of its activation remains unclear. ATR acts together with its partner ATRIP. Using cryo-electron microscopy, we determined the structure of intact Mec1-Ddc2 (the yeast homolog of ATR-ATRIP), which is poised for catalysis, at a resolution of 3. Read More

    [Administering BARS in children with ataxia in a children rehabilitation center in Chiapas, Mexico].
    Rev Med Inst Mex Seguro Soc 2017 Nov-Dec;55(6):715-719
    Centro de Rehabilitación Infantil Teletón, Chiapas, México
    Background: Ataxias are an heterogeneous group of diseases with different etiologies. Scales are used to understand better its natural history and evaluate properly drug efficacy in clinical trials. SARA and ICARS scales have been the most studied and validated so far. Read More

    ATM is required for the prolactin-induced HSP90-mediated increase in cellular viability and clonogenic growth after DNA damage.
    Endocrinology 2017 Nov 24. Epub 2017 Nov 24.
    Department of Biological Sciences, 2500 University Dr NW, University of Calgary, Calgary, AB, T2N 1N4, Canada.
    Prolactin acts as a survival factor for breast cancer cells, but the prolactin signaling pathway and the mechanism is unknown. Previously, we identified the master chaperone, heat shock protein 90α (HSP90α), as a prolactin-Janus-Kinase-(JAK2)-signal-transducer-and-activator-of-transcription-5-(STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of prolactin-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase protein (ATM) plays a critical role in the cellular response to double strand DNA damage. Read More

    Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer.
    Sci Rep 2017 Nov 28;7(1):16475. Epub 2017 Nov 28.
    Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel.
    Ovarian cancer is a highly aggressive disease and novel treatments are required. Thyroid hormones binding to αvβ3 integrin produced growth-promoting activities in ovarian cancer and we hypothesized that natural thyroid hormone derivatives may antagonize these actions. The effect of three antagonists, tetraiodoacetic acid (tetrac), triiodothyroacetic acid (triac) and 3-iodothyronamine (T1AM), on cell proliferation, cell death and DNA damage was studied in two ovarian cancer cell lines (OVCAR3 and A2780), normal hamster ovary control cells (CHOK1) and αvβ3-deficient or transfected HEK293 cells. Read More

    CDYL1 fosters double-strand break-induced transcription silencing and promotes homology-directed repair.
    J Mol Cell Biol 2017 Nov 21. Epub 2017 Nov 21.
    Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
    Cells have evolved DNA damage response (DDR) to repair DNA lesions and thus preserving genomic stability and impeding carcinogenesis. DNA damage induction is accompanied by transient transcription repression. Here, we describe a previously unrecognized role of chromodomain Y-like (CDYL1) protein in fortifying double-strand break (DSB)-induced transcription repression and repair. Read More

    Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer
    Asian Pac J Cancer Prev 2017 11 26;18(11):3003-3009. Epub 2017 Nov 26.
    Jawaharlal Nehru Institute of Advanced Studies (JNIAS), School of Life Sciences, Centre for Biotechnology and Bioinformatics,Secunderabad- 500003,Telangana, India. Email:
    Background: Breast cancer may be induced by activation of protooncogenes to oncogenes and in many cases inactivation of tumor suppressor genes. Ataxia telangiectasia mutated (ATM) is an important tumor suppressor gene which plays central roles in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of double-strand breaks of DNA. In breast cancer, decrease ATM expression correlates with a poor outcome; however, the molecular mechanisms underlying downregulation are still unclear. Read More

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