9,536 results match your criteria Ataxia-telangiectasia


Low Expression of ATM Indicates a Poor Prognosis in Clear Cell Renal Cell Carcinoma.

Clin Genitourin Cancer 2019 Jan 10. Epub 2019 Jan 10.

Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China. Electronic address:

Introduction: The study was carried out to examine the expression of ataxia telangiectasia mutant (ATM) of clear cell renal cell carcinoma (ccRCC), and to explore the relationship between the expression of ATM and the clinicopathologic parameters and prognosis of ccRCC.

Materials And Methods: Clinicopathologic data of the patients with ccRCC were collected from January 2011 to August 2015 in Xiangya Hospital, Central South University. The immunohistochemical method was used to detect the expression of ATM in ccRCC and adjacent tissues. Read More

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http://dx.doi.org/10.1016/j.clgc.2019.01.003DOI Listing
January 2019

ATM mutation spectrum in Russian children with ataxia-telangiectasia.

Eur J Med Genet 2019 Feb 14. Epub 2019 Feb 14.

St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia; I.I. Mechnikov North-Western Medical University, St.-Petersburg, Russia; St.-Petersburg State University, St.-Petersburg, Russia.

Ataxia-telangiectasia (AT) is a severe autosomal recessive orphan disease characterized by a number of peculiar clinical manifestations. Genetic diagnosis of AT is complicated due to a large size of the causative gene, ATM. We used next-generation sequencing (NGS) technology for the ATM analysis in 17 children with the clinical diagnosis of AT. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.02.003DOI Listing
February 2019

Upregulation of long noncoding RNA SNHG20 promotes cell growth and metastasis in esophageal squamous cell carcinoma via modulating ATM-JAK-PD-L1 pathway.

J Cell Biochem 2019 Feb 14. Epub 2019 Feb 14.

Department of Thoracic Surgery, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu, China.

Increasing evidence have proved that long noncoding RNAs (lncRNAs) play significant roles in tumorigenesis and development of various cancers. However, the effect of small nucleolar RNA host gene 20 (SNHG20) on the progression of esophageal squamous cell carcinoma (ESCC) remains to be discovered. Herein, we aim to find out the function and the possible mechanism of SNHG20 in ESCC progression. Read More

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http://dx.doi.org/10.1002/jcb.28444DOI Listing
February 2019

DNA damage as a marker of brain damage in individuals with history of concussions.

Lab Invest 2019 Feb 13. Epub 2019 Feb 13.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Mild traumatic brain injury (mTBI) is common in many populations, including athletes, veterans, and domestic abuse victims. mTBI can cause chronic symptoms, including depression, irritability, memory problems, and attention deficits. A history of repetitive mTBI has been epidemiologically associated with developing early-onset dementia and neurodegenerative diseases and, in particular, is thought to be the underlying cause of chronic traumatic encephalopathy (CTE)-a progressive tauopathy diagnosed by the presence of perivascular hyperphosphorylated tau protein (p-tau) in the depths of cortical sulci. Read More

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http://dx.doi.org/10.1038/s41374-019-0199-8DOI Listing
February 2019

IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response.

Sci Transl Med 2019 Feb;11(479)

Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Patients with glioma whose tumors carry a mutation in isocitrate dehydrogenase 1 (IDH1) are younger at diagnosis and live longer. mutations co-occur with other molecular lesions, such as 1p/19q codeletion, inactivating mutations in the tumor suppressor protein 53 ) gene, and loss-of-function mutations in alpha thalassemia/mental retardation syndrome X-linked gene (). All adult low-grade gliomas (LGGs) harboring ATRX loss also express the IDH1 mutation. Read More

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http://dx.doi.org/10.1126/scitranslmed.aaq1427DOI Listing
February 2019

Clinicopathological significance of ataxia telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3-related (ATR) kinase in MYC overexpressed breast cancers.

Breast Cancer Res Treat 2019 Feb 12. Epub 2019 Feb 12.

Department of Oncology, Nottingham University Hospitals, Nottingham, NG5 1PB, UK.

Purpose: MYC transcription factor has critical roles in cell growth, proliferation, metabolism, differentiation, transformation and angiogenesis. MYC overexpression is seen in about 15% of breast cancers and linked to aggressive phenotypes. MYC overexpression also induces oxidative stress and replication stress in cells. Read More

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http://dx.doi.org/10.1007/s10549-018-05113-8DOI Listing
February 2019

Atrophy, oxidative switching and ultrastructural defects in skeletal muscle of Ataxia Telangiectasia mouse model.

J Cell Sci 2019 Feb 11. Epub 2019 Feb 11.

Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University, Rome, Italy

Ataxia Telangiectasia is a rare, multi system disease caused by ATM kinase deficiency. knockout mice recapitulate premature aging, immunodeficiency, cancer predisposition, growth retardation and motor defects but not cerebellar neurodegeneration and ataxia. We explored if Atm loss is responsible of skeletal muscle defects by investigating myofiber morphology, oxidative/glycolytic activity, myocyte ultrastructural architecture and neuromuscular junctions. Read More

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http://dx.doi.org/10.1242/jcs.223008DOI Listing
February 2019

Effects of aflatoxin B on the cell cycle distribution of splenocytes in chickens.

J Toxicol Pathol 2019 Jan 18;32(1):27-36. Epub 2018 Nov 18.

College of Veterinary Medicine, Sichuan Agricultural University, No. 211 Huimin Road, Wenjiang District, Chengdu, Sichuan 611130, P.R. China.

The purpose of the present study was to evaluate effects of aflatoxin B (AFB) on the cell cycle and proliferation of splenic cells in chickens. A total of 144 one-day-old Cobb male chickens were randomly divided into 2 equal groups of 72 each and were fed on diets as follows: a control diet and a 0.6 mg/kg AFB diet for 21 days. Read More

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https://www.jstage.jst.go.jp/article/tox/32/1/32_2018-0015/_
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http://dx.doi.org/10.1293/tox.2018-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361662PMC
January 2019
1 Read

Loss of the tumor suppressor BIN1 enables ATM Ser/Thr kinase activation by the nuclear protein E2F1 and renders cancer cells resistant to cisplatin.

J Biol Chem 2019 Feb 7. Epub 2019 Feb 7.

Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University, United States.

The tumor suppressor bridging integrator 1 (BIN1) is a corepressor of the transcription factor E2F1 and inhibits cell-cycle progression. BIN1 also curbs cellular poly(ADP-ribosyl)ation (PARylation) and increases sensitivity of cancer cells to DNA-damaging therapeutic agents such as cisplatin. However, how BIN1 deficiency, a hallmark of advanced cancer cells, increases cisplatin resistance remains elusive. Read More

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http://dx.doi.org/10.1074/jbc.RA118.005699DOI Listing
February 2019

Excess growth hormone suppresses DNA damage repair in epithelial cells.

JCI Insight 2019 Feb 7;4(3). Epub 2019 Feb 7.

Pituitary Center.

Growth hormone (GH) decreases with age, and GH therapy has been advocated by some to sustain lean muscle mass and vigor in aging patients and advocated by athletes to enhance performance. Environmental insults and aging lead to DNA damage, which - if unrepaired - results in chromosomal instability and tumorigenesis. We show that GH suppresses epithelial DNA damage repair and blocks ataxia telangiectasia mutated (ATM) kinase autophosphorylation with decreased activity. Read More

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http://dx.doi.org/10.1172/jci.insight.125762DOI Listing
February 2019

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models.

Mol Cells 2019 Feb 1. Epub 2019 Feb 1.

Well Aging Research Center.

The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. Read More

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http://dx.doi.org/10.14348/molcells.2018.0352DOI Listing
February 2019
1 Read

A tumor suppressive DNA translocase named FANCM.

Crit Rev Biochem Mol Biol 2019 Feb 4:1-14. Epub 2019 Feb 4.

a Institute of Human Genetics (IGH), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM) , Montpellier , France.

FANCM is named after Fanconi anemia (FA) complement group M. The clinical symptoms of FA include congenital abnormalities, pancytopenia, and cancer proneness. However, recent studies reveal that biallelic inactivation of FANCM does not cause the constellation of FA symptoms, but predisposes patients to cancer and infertility. Read More

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http://dx.doi.org/10.1080/10409238.2019.1568963DOI Listing
February 2019
2 Reads

Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes.

Toxicol Res (Camb) 2019 Jan 15;8(1):15-24. Epub 2018 Nov 15.

Department of Health Toxicology , Xiangya School of Public Health , Central South University , Changsha 410078 , PR China . Email: ; Tel: +86 -731-84487130.

Previous evidence revealed significant elevated liver cancer mortality in the areas where water was contaminated with hexavalent chromium [Cr(vi)], which highlighted that we should pay more attention to Cr(vi)-induced cytotoxicity in hepatocytes. We found that Clusterin (CLU) was up-regulated in Cr(vi)-exposed L-02 hepatocytes, but the role CLU played in Cr(vi)-induced cytotoxicity has never been explored. In the present study, we demonstrate Cr(vi) targeted mitochondrial respiratory chain complex I (MRCC I) activity and induced reactive oxygen species (ROS) accumulation, which caused mitochondrial damage that was characterized by the increase of permeability transition pore (PTP) open rate, the collapse of mitochondrial membrane potential (MMP), and the release of apoptosis-inducing factor (AIF) and Cytochrome C (Cyt C) from mitochondria to cytoplasm, which then induced cell viability loss and increased aspartate transaminase (AST)/alanine transaminase (ALT) leakage. Read More

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http://dx.doi.org/10.1039/c8tx00231bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334495PMC
January 2019

PP2ACα deficiency impairs early cortical development through inducing DNA damage in neuroprojenitor cells.

Int J Biochem Cell Biol 2019 Jan 30;109:40-58. Epub 2019 Jan 30.

National Institute of Neurological Disorders and Stroke, National Institute of Heath, Bethesda, USA. Electronic address:

The role of protein phosphatase 2ACα (PP2ACα) in brain development is poorly understood. To understand the function of PP2ACα in neurogenesis, we inactivated Pp2acα gene in the central nervous system (CNS) of mice by Cre/LoxP system and generated the PP2ACα deficient mice (designated as the Pp2acα mice). PP2ACα deletion results in DNA damage in neuroprogenitor cells (NPCs), which impairs memory formation and cortical neurogenesis. Read More

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http://dx.doi.org/10.1016/j.biocel.2019.01.021DOI Listing
January 2019
2 Reads
4.046 Impact Factor

ATM rs189037 (G > A) polymorphism increased the risk of cancer: an updated meta-analysis.

BMC Med Genet 2019 Feb 1;20(1):28. Epub 2019 Feb 1.

School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110122, China.

Background: Rs189037 (G > A) is a functional single nucleotide polymorphism (SNP) in the Ataxia-telangiectasia mutated (ATM) gene that may be associated with the risk of cancer. We performed a meta-analysis to determine whether rs189037 polymorphism influences the occurrence of cancer and examined the relationship between this SNP and the etiology of cancer.

Methods: Case-control studies were retrieved from literature databases in accordance with established inclusion criteria. Read More

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http://dx.doi.org/10.1186/s12881-019-0760-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359756PMC
February 2019
3 Reads

ATM phosphorylation of the actin-binding protein drebrin controls oxidation stress-resistance in mammalian neurons and C. elegans.

Nat Commun 2019 Jan 30;10(1):486. Epub 2019 Jan 30.

Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Drebrin (DBN) regulates cytoskeletal functions during neuronal development, and is thought to contribute to structural and functional synaptic changes associated with aging and Alzheimer's disease. Here we show that DBN coordinates stress signalling with cytoskeletal dynamics, via a mechanism involving kinase ataxia-telangiectasia mutated (ATM). An excess of reactive oxygen species (ROS) stimulates ATM-dependent phosphorylation of DBN at serine-647, which enhances protein stability and accounts for improved stress resilience in dendritic spines. Read More

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http://www.nature.com/articles/s41467-019-08420-w
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http://dx.doi.org/10.1038/s41467-019-08420-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353951PMC
January 2019
3 Reads

Ataxia-telangiectasia: A review of clinical features and molecular pathology.

Pediatr Allergy Immunol 2019 Jan 27. Epub 2019 Jan 27.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran, and the University of Medical Science, Tehran, Iran.

Ataxia telangiectasia (A-T) is an autosomal recessive primary immunodeficiency (PID) disease that is caused by mutations in ataxia telangiectasia mutated (ATM) gene encoding a serine/threonine protein kinase. A-T patients represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, susceptibility to malignancies and increased metabolic diseases. This congenital disorder has phenotypic heterogeneity, and the severity of symptoms varies in different patients based on severity of mutations and disease progression. Read More

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http://dx.doi.org/10.1111/pai.13020DOI Listing
January 2019
1 Read
3.397 Impact Factor

Testing the Neuroprotective Properties of PCSO-524 Using a Neuronal Cell Cycle Suppression Assay.

Mar Drugs 2019 Jan 24;17(2). Epub 2019 Jan 24.

Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Cell cycle reentry is a unified mechanism shared by several neurodegenerative diseases, including Alzheimer's disease (AD) and Ataxia Telangiectasia (A-T). This phenotype is often related to neuroinflammation in the central nervous system. To mimic brain inflammation in vitro, we adopted the previously established method of using conditioned medium collected from activated THP-1 cells and applied it to both differentiated HT22 cells and primary neurons. Read More

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http://dx.doi.org/10.3390/md17020079DOI Listing
January 2019

DNA damage and transcriptional regulation in iPSC-derived neurons from Ataxia Telangiectasia patients.

Sci Rep 2019 Jan 24;9(1):651. Epub 2019 Jan 24.

Department of Research, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Via Amadeo 42, 20133, Milano, Italy.

Ataxia Telangiectasia (A-T) is neurodegenerative syndrome caused by inherited mutations inactivating the ATM kinase, a master regulator of the DNA damage response (DDR). What makes neurons vulnerable to ATM loss remains unclear. In this study we assessed on human iPSC-derived neurons whether the abnormal accumulation of DNA-Topoisomerase 1 adducts (Top1ccs) found in A-T impairs transcription elongation, thus favoring neurodegeneration. Read More

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http://dx.doi.org/10.1038/s41598-018-36912-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346060PMC
January 2019
5.078 Impact Factor

Knockdown of RNF2 enhances radiosensitivity of lung squamous cell carcinoma cells.

Biochem Cell Biol 2019 Jan 23. Epub 2019 Jan 23.

The Fourth Hospital of Hebei Medical University, Department of Radiotherapy , 12 Jiankang Road , Shijiazhuang, China , 050011 ;

A previous study has reported that RING finger protein 2 (RNF2) knockdown increases radiosensitivity of esophageal cancer cells both in vitro and in vivo. However, the effect of RNF2 knockdown on radiosensitivity in squamous cell carcinoma (SqCC) remains unknown. NCI-H226 and SK-MES-1 cells were exposed to X-ray irradiation and then RNF2 levels were determined. Read More

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http://www.nrcresearchpress.com/doi/10.1139/bcb-2018-0252
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http://dx.doi.org/10.1139/bcb-2018-0252DOI Listing
January 2019
4 Reads

GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells.

Cell Death Differ 2019 Jan 22. Epub 2019 Jan 22.

Instituto de Investigaciones Biomédicas CSIC/UAM, IDiPaz, C/ Arturo Duperier, 4, 28029, Madrid, Spain.

Ataxia telangiectasia (AT) is a genetic disease caused by mutations in the ATM gene but the mechanisms underlying AT are not completely understood. Key functions of the ATM protein are to sense and regulate cellular redox status and to transduce DNA double-strand break signals to downstream effectors. ATM-deficient cells show increased ROS accumulation, activation of p38 protein kinase, and increased levels of DNA damage. Read More

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http://dx.doi.org/10.1038/s41418-018-0272-7DOI Listing
January 2019
1 Read

Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence.

Int J Mol Sci 2019 Jan 21;20(2). Epub 2019 Jan 21.

Laboratory of Physiological Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.

Bacteria inhabiting the human gut metabolize microbiota-accessible carbohydrates (MAC) contained in plant fibers and subsequently release metabolic products. Gut bacteria produce hydrogen (H₂), which scavenges the hydroxyl radical (•OH). Because H₂ diffuses within the cell, it is hypothesized that H₂ scavenges cytoplasmic •OH (cyto •OH) and suppresses cellular senescence. Read More

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http://dx.doi.org/10.3390/ijms20020456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359316PMC
January 2019

ATR activated by EB virus facilitates chemotherapy resistance to cisplatin or 5-fluorouracil in human nasopharyngeal carcinoma.

Cancer Manag Res 2019 9;11:573-585. Epub 2019 Jan 9.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China,

Purpose: Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and increases the chemotherapy resistance of tumor cells. Although the mechanism by which EBV manipulates ataxia telangiectasia mutation (ATM)-mediated DNA damage response in NPC has been extensively studied, the relationship between ATR (ATM and Rad-3 related) and EBV infection is largely unexplored, and also the role of ATR in chemotherapy resistance in EBV-positive NPC has not been specifically reported.

Materials And Methods: Levels of γ-H2AX, latent membrane protein 1 (LMP1), and EBV-encoded RNA in clinical NPC and nasopharyngeal inflammation (NPI) specimens were examined using immunohistochemistry and in situ hybridization. Read More

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http://dx.doi.org/10.2147/CMAR.S187099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331066PMC
January 2019
3 Reads

Epstein-Barr Virus (EBV)-Related Lymphoproliferative Disorders in Ataxia Telangiectasia: Does ATM Regulate EBV Life Cycle?

Front Immunol 2018 4;9:3060. Epub 2019 Jan 4.

INSERM U1163/CNRS ERL8254 - Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, IMAGINE Institute, Paris, France.

Epstein-Barr virus (EBV) is an ubiquitous herpesvirus with a tropism for epithelial cells (where lytic replication occurs) and B-cells (where latency is maintained). EBV persists throughout life and chronic infection is asymptomatic in most individuals. However, immunocompromised patients may be unable to control EBV infection and are at increased risk of EBV-related malignancies, such as diffuse large B-cell lymphomas or Hodgkin's lymphomas. Read More

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http://dx.doi.org/10.3389/fimmu.2018.03060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329310PMC
January 2019
3 Reads

Type 1 diabetes upregulates metastasis-associated protein 1- phosphorylated histone 2AX signaling in the testis.

Eur J Pharmacol 2019 Mar 16;846:30-37. Epub 2019 Jan 16.

Department of Anatomy, Faculty of Medicine, Health Science Center, Kuwait University, Kuwait.

Under the sustained hyperglycemic state, oxidative stress induces irreparable DNA double-strand breaks resulting in germ cell death and testicular atrophy. Although molecular mechanisms underlying DNA damage repair in testicular cells are gradually getting unraveled, the effects on DNA double-strand breaks sensing are not precisely known. In this study, using streptozotocin-induced type 1 diabetic rats, we report that hyperglycemic state for one month or three months does not increase the levels of ataxia telangiectasia mutated (ATM) protein- an upstream kinase responsible for the phosphorylation of histone 2AX (Ɣ-H2AX)- after the formation of DNA double-strand breaks. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00142999193002
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http://dx.doi.org/10.1016/j.ejphar.2019.01.019DOI Listing
March 2019
6 Reads

Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor.

Int J Mol Sci 2019 Jan 16;20(2). Epub 2019 Jan 16.

Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy.

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as "synthetic torpor" in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Read More

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http://dx.doi.org/10.3390/ijms20020352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359347PMC
January 2019
1 Read

ATDC mediates a TP63-regulated basal cancer invasive program.

Oncogene 2019 Jan 14. Epub 2019 Jan 14.

Department of Surgery, NYU Langone Health, New York, NY, 10016, USA.

Basal subtype cancers are deadly malignancies but the molecular events driving tumor lethality are not completely understood. Ataxia-telangiectasia group D complementing gene (ATDC, also known as TRIM29), is highly expressed and drives tumor formation and invasion in human bladder cancers but the factor(s) regulating its expression in bladder cancer are unknown. Molecular subtyping of bladder cancer has identified an aggressive basal subtype, which shares molecular features of basal/squamous tumors arising in other organs and is defined by activation of a TP63-driven gene program. Read More

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http://dx.doi.org/10.1038/s41388-018-0646-9DOI Listing
January 2019
1 Read

ATM is activated by ATP depletion and modulates mitochondrial function through NRF1.

J Cell Biol 2019 Jan 14. Epub 2019 Jan 14.

Division of Life Science and The State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong

Ataxia-telangiectasia (A-T) is an autosomal recessive disease caused by mutation of the gene and is characterized by loss of cerebellar Purkinje cells, neurons with high physiological activity and dynamic ATP demands. Here, we show that depletion of ATP generates reactive oxygen species that activate ATM. We find that when ATM is activated by oxidative stress, but not by DNA damage, ATM phosphorylates NRF1. Read More

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http://www.jcb.org/lookup/doi/10.1083/jcb.201806197
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http://dx.doi.org/10.1083/jcb.201806197DOI Listing
January 2019
9 Reads

IL-1β Inflammatory Cytokine-Induced Isoform ∆NP63α Signaling Cascade Contributes to Cisplatin Resistance in Human Breast Cancer Cells.

Int J Mol Sci 2019 Jan 11;20(2). Epub 2019 Jan 11.

Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto, Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico.

The mechanisms behind the induction of malignancy and chemoresistance in breast cancer cells are still not completely understood. Inflammation is associated with the induction of malignancy in different types of cancer and is highlighted as an important factor for chemoresistance. In previous work, we demonstrated that the inflammatory cytokine interleukin 1β (IL-1β)-induced upregulation of genes was associated with chemoresistance in breast cancer cells. Read More

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http://www.mdpi.com/1422-0067/20/2/270
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http://dx.doi.org/10.3390/ijms20020270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358904PMC
January 2019
3 Reads

A novel ATM mutation associated with elevated atypical lymphocyte populations, hyper-IgM, and cutaneous granulomas.

Clin Immunol 2019 Jan 9;200:55-63. Epub 2019 Jan 9.

Immunodeficiency Diagnosis and Treatment Program, Department of Pediatrics, National Jewish Health, Denver, CO 80206, United States. Electronic address:

Ataxia-Telangiectasia (AT) is an immunodeficiency most often associated with T cell abnormalities. We describe a patient with a hyper-IgM phenotype and immune cell abnormalities that suggest a distinct clinical phenotype. Significant B cell abnormalities with increased unswitched memory B cells, decreased naive transitional B cells, and an elevated frequency of CD19CD38CD27CD10CD21 B cells expressing high levels of T-bet and Fas were demonstrated. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15216616183062
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http://dx.doi.org/10.1016/j.clim.2019.01.002DOI Listing
January 2019
6 Reads

Topoisomerase IIβ-binding protein 1 activates expression of E2F1 and p73 in HPV-positive cells for genome amplification upon epithelial differentiation.

Oncogene 2019 Jan 10. Epub 2019 Jan 10.

Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

High-risk human papillomaviruses (HPVs) constitutively activate ataxia telangiectasia mutated (ATM) and ataxia telangiectasia- and Rad3-related (ATR) DNA damage repair pathways for viral genome amplification. HPVs activate these pathways through the immune regulator STAT-5. For the ATR pathway, STAT-5 increases expression of the topoisomerase IIβ-binding protein 1 (TopBP1), a scaffold protein that binds ATR and recruits it to sites of DNA damage. Read More

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http://www.nature.com/articles/s41388-018-0633-1
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http://dx.doi.org/10.1038/s41388-018-0633-1DOI Listing
January 2019
3 Reads
8.459 Impact Factor

Association Between Impairment of DNA Double Strand Break Repair and Decreased Ovarian Reserve in Patients With Endometriosis.

Front Endocrinol (Lausanne) 2018 21;9:772. Epub 2018 Dec 21.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Repair of DNA double strand break (DSB) is an important mechanism for maintaining genetic stability during a DNA damage event. Although, a growing body of recent evidence suggests that DNA DSBs and related repair mechanisms may be important in ovarian aging and in various cancers, there are few reports in endometriosis. We, therefore, examined expression levels of genes pertaining to DNA DSB repair in patients with endometriosis to assess the potential effects on ovarian reserves. Read More

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https://www.frontiersin.org/article/10.3389/fendo.2018.00772
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http://dx.doi.org/10.3389/fendo.2018.00772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308303PMC
December 2018
3 Reads

DNA Damage Response Signals Transduce Stress From Rheumatoid Arthritis Risk Factors Into T Cell Dysfunction.

Authors:
Lan Shao

Front Immunol 2018 20;9:3055. Epub 2018 Dec 20.

The Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Rheumatoid arthritis (RA) is an autoimmune-mediated disease that is associated with significant cartilage damage and immunosenescence. Despite decades of research, the major signal pathways that initiate RA are still unclear. The DNA damage response (DDR) is a specific and hierarchical network that includes cell cycle checkpoints, DNA repair, and DNA-damage tolerance pathways. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.03055
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http://dx.doi.org/10.3389/fimmu.2018.03055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306440PMC
December 2018
7 Reads

Versatility of the Mec1 signaling network in mediating resistance to replication, genotoxic, and proteotoxic stresses.

Curr Genet 2019 Jan 5. Epub 2019 Jan 5.

School of Medical Sciences and North West Cancer Research Institute, Bangor University, Bangor, LL57 2UW, UK.

The ataxia-telangiectasia mutated/ATM and Rad3-related (ATM/ATR) family proteins are evolutionarily conserved serine/threonine kinases best known for their roles in mediating the DNA damage response. Upon activation, ATM/ATR phosphorylate numerous targets to stabilize stalled replication forks, repair damaged DNA, and inhibit cell cycle progression to ensure survival of the cell and safeguard integrity of the genome. Intriguingly, separation of function alleles of the human ATM and MEC1, the budding yeast ATM/ATR, were shown to confer widespread protein aggregation and acute sensitivity to different types of proteotoxic agents including heavy metal, amino acid analogue, and an aggregation-prone peptide derived from the Huntington's disease protein. Read More

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http://link.springer.com/10.1007/s00294-018-0920-y
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http://dx.doi.org/10.1007/s00294-018-0920-yDOI Listing
January 2019
4 Reads

A historical reflection on our understanding of radiation-induced DNA double strand break repair in somatic mammalian cells; interfacing the past with the present.

Int J Radiat Biol 2019 Jan 4:1-36. Epub 2019 Jan 4.

b Genome Damage and Stability Centre, School of Life Sciences, University of Sussex , Brighton , BN19RQ , UK.

Purpose: The International Journal of Radiation Biology (IJRB) is celebrating 60 years of publishing in 2019. IJRB has made an enormous contribution to publishing papers that have enhanced our understanding of the DNA damage response (DDR) activated following exposure to ionising radiation (IR). The IR-induced DDR field has a rich history but many outstanding papers pass unread by young scientists overwhelmed by the current literature. Read More

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http://dx.doi.org/10.1080/09553002.2018.1564083DOI Listing
January 2019

Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders.

J Clin Immunol 2019 Jan 3;39(1):81-89. Epub 2019 Jan 3.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Department of Pediatrics, University of Washington, Seattle, WA, USA.

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). Read More

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http://link.springer.com/10.1007/s10875-018-0581-0
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http://dx.doi.org/10.1007/s10875-018-0581-0DOI Listing
January 2019
6 Reads

Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients.

Breast Cancer Res Treat 2019 Jan 3. Epub 2019 Jan 3.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, 100142, Beijing, People's Republic of China.

Purpose: The ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients. Read More

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http://dx.doi.org/10.1007/s10549-018-05124-5DOI Listing
January 2019
2 Reads

Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy.

J Gastrointest Oncol 2018 Dec;9(6):1198-1206

Department of Medicine, Samsung Medical Center, Seoul, Korea.

Background: Gastric cancer (GC) is a leading cause of cancer-specific mortality with limited biologically informed treatments. The ataxia telangiectasia mutated () gene is critically involved in the repair of double-stranded DNA breaks and a component of DNA damage repair (DDR) pathways. Platinum salts are hypothesized to have increased efficacy in tumors deficient in DDR pathways. Read More

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http://dx.doi.org/10.21037/jgo.2018.09.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286926PMC
December 2018
1 Read

Linking the organization of DNA replication with genome maintenance.

Curr Genet 2019 Jan 2. Epub 2019 Jan 2.

CNRS, University of Rennes, Institute of Genetics and Development of Rennes, 35043, Rennes, France.

The spatial and temporal organization of genome duplication, also referred to as the replication program, is defined by the distribution and the activities of the sites of replication initiation across the genome. Alterations to the replication profile are associated with cell fate changes during development and in pathologies, but the importance of undergoing S phase with distinct and specific programs remains largely unexplored. We have recently addressed this question, focusing on the interplay between the replication program and genome maintenance. Read More

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http://dx.doi.org/10.1007/s00294-018-0923-8DOI Listing
January 2019
1 Read

ATM activation is impaired in human cells defective in RecQL4 helicase activity.

Biochem Biophys Res Commun 2019 Feb 26;509(2):379-383. Epub 2018 Dec 26.

Department of Biology Education, Seoul National University, Seoul, 08826, South Korea; Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul, 08826, South Korea. Electronic address:

RecQL4 has been shown to be involved in DNA replication and repair, but its role in DNA damage checkpoint pathway has not been reported. Here, we show that RecQL4 plays an important role in the activation of ataxia telangiectasia mutated (ATM)-dependent checkpoint pathway in human cells. Cells depleted with RecQL4 or Rothmund-Thomson syndrome cells showed significant impairment in the activation of ATM and the downstream effector proteins such as checkpoint kinase 2 and p53 after DNA damage. Read More

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http://dx.doi.org/10.1016/j.bbrc.2018.12.151DOI Listing
February 2019

DNA damage checkpoint response to aflatoxin B1.

Environ Toxicol Pharmacol 2019 Jan 7;65:90-96. Epub 2018 Dec 7.

Gazi University, Faculty of Medicine, Department of General Surgery, Ankara, Turkey.

Although most countries regulate the aflatoxin levels in food by legislations, high amounts of aflatoxin B1 (AFB1)-DNA adducts can still be detected in normal and tumorous tissue obtained from cancer patients. AFB1 cannot directly interact with DNA unless it is biotransformed to AFB1-8, 9-epoxide via cytochrome p450 enzymes. This metabolite spontaneously and irreversibly attaches to guanine residues to generate highly mutagenic DNA adducts. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13826689183029
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http://dx.doi.org/10.1016/j.etap.2018.12.006DOI Listing
January 2019
8 Reads

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia.

PLoS One 2018 26;13(12):e0209496. Epub 2018 Dec 26.

Eudowood Division of Pediatric, Allergy and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.

Introduction: Classic ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by early onset ataxia, immune deficiency, sino-pulmonary disease, lymphoid/solid malignancies and telangiectasias. Prior studies have suggested that chronic inflammation and premature aging may contribute to the development of malignancy and pulmonary disease in people with A-T. To further examine the link between A-T and inflammation, we hypothesized that subjects with classic A-T would have greater enrichment of inflammatory pathways in peripheral blood mononuclear cells (PBMCs) compared to non A-T age-matched controls. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209496PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306200PMC
December 2018
3.234 Impact Factor

Ataxia-telangiectasia-like disorder in a family deficient for MRE11A, caused by a variant.

Neurol Genet 2018 Dec 3;4(6):e295. Epub 2018 Dec 3.

Medical Genetics Laboratory (M. Sedghi), Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurology (M. Salari), Shahid Beheshti University of Medical Science, Tehran, Iran; Department of Pathology (A.-R.M.), University of Gothenburg, Sahlgrenska University Hospital, Sweden; Kariminejad-Najmabadi Pathology & Genetics Center (A.K.), Tehran, Iran; Department of Diagnostic Genomics (M.D.), Pathwest, QEII Medical Centre; Centre for Medical Research (H.G., N.L., H.T.), The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Australia; School of Bioscience (B.O.), University of Skovde; and Division Biomedicine (H.T.), School of Health and Education, University of Skovde, Sweden.

Objective: We report 3 siblings with the characteristic features of ataxia-telangiectasia-like disorder associated with a homozygous synonymous variant causing nonsense-mediated mRNA decay (NMD) and MRE11A deficiency.

Methods: Clinical assessments, next-generation sequencing, transcript and immunohistochemistry analyses were performed.

Results: The patients presented with poor balance, developmental delay during the first year of age, and suffered from intellectual disability from early childhood. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283458PMC
December 2018
1 Read

Variant ataxia-telangiectasia with prominent camptocormia.

Parkinsonism Relat Disord 2018 Dec 17. Epub 2018 Dec 17.

Department of Neurology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

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https://linkinghub.elsevier.com/retrieve/pii/S13538020183055
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http://dx.doi.org/10.1016/j.parkreldis.2018.12.017DOI Listing
December 2018
8 Reads
3.972 Impact Factor

Cordycepin, isolated from medicinal fungus Cordyceps sinensis, enhances radiosensitivity of oral cancer associated with modulation of DNA damage repair.

Food Chem Toxicol 2019 Feb 18;124:400-410. Epub 2018 Dec 18.

Institute of Tradition Medicine, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, 25160, Taiwan; Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, 25160, Taiwan; Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung, 40402, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan. Electronic address:

Concurrent chemotherapy and radiotherapy (RT) is important for controlling oral squamous cell carcinoma (OSCC), which is often accompanied by significant acute and late toxicities. We investigated whether cordycepin, a small molecule extracted from Cordyceps sinensis, could enhance the radiosensitivity of oral cancer cells. Using colony formation assay, we demonstrated that cordycepin induces radiosensitizing effects on two OSCC cells. Read More

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http://dx.doi.org/10.1016/j.fct.2018.12.025DOI Listing
February 2019
1 Read

Long Noncoding RNA FAM201A Mediates the Radiosensitivity of Esophageal Squamous Cell Cancer by Regulating ATM and mTOR Expression via miR-101.

Front Genet 2018 5;9:611. Epub 2018 Dec 5.

Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China.

The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC. Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive ( = 3) and radioresistant ( = 3) ESCC tumor tissues. Read More

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https://www.frontiersin.org/article/10.3389/fgene.2018.00611
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http://dx.doi.org/10.3389/fgene.2018.00611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292217PMC
December 2018
8 Reads

XRCC2 Regulates Replication Fork Progression during dNTP Alterations.

Cell Rep 2018 Dec;25(12):3273-3282.e6

Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. Electronic address:

RAD51 paralogs are essential for maintenance of genomic integrity through protection of stalled replication forks and homology-directed repair (HDR) of double-strand breaks. Here, we find that a subset of RAD51 paralogs, XRCC2 (FANCU) and its binding partner RAD51D, restrain active DNA synthesis during dinucleotide triphosphate (dNTP) alterations in a manner independent of HDR. The absence of XRCC2 is associated with increased levels of RRM2, the regulatory subunit of ribonucleotide reductase (RNR), and concomitantly high nucleotide pools, leading to unrestrained fork progression and accumulation of DNA damage during dNTP alterations. Read More

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http://dx.doi.org/10.1016/j.celrep.2018.11.085DOI Listing
December 2018

ATM-Mediated Phosphorylation of Cortactin Involved in Actin Polymerization Promotes Breast Cancer Cells Migration and Invasion.

Cell Physiol Biochem 2018 14;51(6):2972-2988. Epub 2018 Dec 14.

Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing,

Background/aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear.

Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Read More

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http://dx.doi.org/10.1159/000496048DOI Listing
January 2019
2.875 Impact Factor