625 results match your criteria Nijmegen Breakage Syndrome


Radiogenomics.

Med Phys 2018 Nov;45(11):e1111-e1122

Trento Institute for Fundamental Physics Applications, National Institute for Nuclear Physics, Trento, Italy.

Purpose: Radiogenomics is the study of genomic changes that underlie the radioresponse of normal and tumor tissues. And while this is generally regarded as a whole genome approach, one must keep in mind the impact of single gene biology on radioresponse, (ataxia telangiectasia, Nijmegen breakage syndrome).

Methods: This review begins with the association of single nucleotide polymorphisms in the DNA with adverse normal tissue events to the prediction of therapeutic outcome after radiotherapy. Read More

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http://doi.wiley.com/10.1002/mp.13064
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http://dx.doi.org/10.1002/mp.13064DOI Listing
November 2018
3 Reads

Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.

Pediatrics 2018 Oct 12;142(4). Epub 2018 Sep 12.

Departments of Pulmonology and Allergy and

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease characterized by microcephaly, growth retardation, severe immunodeficiency, and predisposition to lymphoid malignancy. In this report, we describe a case of a 9-year-old boy, previously diagnosed with NBS and symptoms of dyspnea, dry cough, and fever. Despite initial recognition of pneumonia, there was no response to broad spectrum antimicrobial treatment, negative results from microbiological tests, and unclear changes in lung imaging were observed. Read More

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http://dx.doi.org/10.1542/peds.2018-0122DOI Listing
October 2018
1 Read

Case 1: Microcephaly, Skeletal Dysplasia, and Immunodeficiency in a Newborn.

Pediatr Rev 2018 Jul;39(7):359-362

Department of Medical Genetics and Genomic Medicine, Saint Peter's University Hospital, New Brunswick, NJ.

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http://dx.doi.org/10.1542/pir.2017-0101DOI Listing
July 2018
1 Read

Poly(ADP-ribose) polymerase-1 promotes recruitment of meiotic recombination-11 to chromatin and DNA double-strand break repair in Ku70-deficient breast cancer cells.

FASEB J 2018 Jun 6:fj201800092R. Epub 2018 Jun 6.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Poly(ADP-ribose) polymerase (PARP)-1 may act in an error-prone pathway called alternative end joining (Alt-EJ) for DNA double-strand break (DSB) repair when nonhomologous end joining is defective. We examined the recruitment of PARP-1 to chromatin in response to radiomimetic agents and the effects of PARP-1 inhibition on DSB repair and recruitment of the meiotic recombination (MRE)-11-double-strand break repair (RAD50) protein-Nijmegen breakage syndrome (NSB)-1 (MRN) complex to the chromatin in Ku70-deficient breast cancer cells. The chromatin-binding affinity of PARP-1 was enhanced in response to neocarzinostatin (NCS) or calicheamicin treatment in the absence of Ku70. Read More

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http://dx.doi.org/10.1096/fj.201800092RDOI Listing

The Major Tegument Protein of Bovine Herpesvirus 1, VP8, Interacts with DNA Damage Response Proteins and Induces Apoptosis.

J Virol 2018 08 17;92(15). Epub 2018 Jul 17.

VIDO-InterVac, University of Saskatchewan, Saskatoon, SK, Canada

VP8, the gene product in bovine herpesvirus-1 (BoHV-1), is a major tegument protein that is essential for virus replication The major DNA damage response protein, ataxia telangiectasia mutated (ATM), phosphorylates Nijmegen breakage syndrome (NBS1) and structural maintenance of chromosome-1 (SMC1) proteins during the DNA damage response. VP8 was found to interact with ATM and NBS1 during transfection and BoHV-1 infection. However, VP8 did not interfere with phosphorylation of ATM in transfected or BoHV-1-infected cells. Read More

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http://dx.doi.org/10.1128/JVI.00773-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052309PMC
August 2018
14 Reads

Correction to: Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.

J Clin Immunol 2018 May;38(4):538

Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands.

The original version of the article, "Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence" incorrectly listed the affiliation of the fourth author, Iwona Solarska. The correct affiliation is "Molecular Biology Laboratory, Institute of Hematology and Transfusion Medicine. Read More

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http://dx.doi.org/10.1007/s10875-018-0503-1DOI Listing
May 2018
2 Reads

The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.

Annu Rev Biochem 2018 Jun 25;87:263-294. Epub 2018 Apr 25.

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA; email: ,

Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette-ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11-RAD50-NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076887PMC
June 2018
2 Reads

Identification of variants in pleiotropic genes causing "isolated" premature ovarian insufficiency: implications for medical practice.

Eur J Hum Genet 2018 Sep 30;26(9):1319-1328. Epub 2018 Apr 30.

Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.

Next-generation sequencing (NGS) is increasingly being used in a clinical setting for the molecular diagnosis of patients with heterogeneous disorders, such as premature ovarian insufficiency (POI). We performed NGS of ~1000 candidate genes in four unrelated patients with POI. We discovered the genetic cause of "isolated" POI in two cases, both of which had causative variants in surprising genes. Read More

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http://dx.doi.org/10.1038/s41431-018-0140-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117257PMC
September 2018
1 Read

Association of 17q24.2-q24.3 deletions with recognizable phenotype and short telomeres.

Am J Med Genet A 2018 Jun 25;176(6):1438-1442. Epub 2018 Apr 25.

Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.

Microdeletions of 17q24.2-q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. Read More

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http://dx.doi.org/10.1002/ajmg.a.38711DOI Listing
June 2018
6 Reads

Interdependent and separable functions of MRN-C complex members couple formation and repair of meiotic DSBs.

Proc Natl Acad Sci U S A 2018 05 23;115(19):E4443-E4452. Epub 2018 Apr 23.

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305;

Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Read More

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http://dx.doi.org/10.1073/pnas.1719029115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948970PMC

Genetic testing for hereditary prostate cancer: Current status and limitations.

Cancer 2018 Aug 18;124(15):3105-3117. Epub 2018 Apr 18.

Department of Urology, Yale School of Medicine, New Haven, Connecticut.

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. Read More

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http://dx.doi.org/10.1002/cncr.31316DOI Listing
August 2018
2 Reads

Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia-Telangiectasia and Nijmegen Breakage Syndrome.

Oxid Med Cell Longev 2017 31;2017:6745840. Epub 2017 Dec 31.

Department of Pediatrics Rheumatology, Immunology, and Metabolic Bone Diseases, Medical University of Bialystok, Waszyngtona 17 Str., 15-274 Bialystok, Poland.

This study compared the antioxidant status and major lipophilic antioxidants in patients with ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS). Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and concentrations of coenzyme Q10 (CoQ10) and vitamins A and E were estimated in the plasma of 22 patients with AT, 12 children with NBS, and the healthy controls. In AT patients, TAS (median 261. Read More

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http://dx.doi.org/10.1155/2017/6745840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804414PMC
October 2018
10 Reads

Evidence for a pre-malignant cell line in a skin biopsy from a patient with Nijmegen breakage syndrome.

Mol Cytogenet 2018 7;11:17. Epub 2018 Feb 7.

4Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.

Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence. Read More

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https://molecularcytogenetics.biomedcentral.com/articles/10.
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http://dx.doi.org/10.1186/s13039-018-0364-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803995PMC
February 2018
13 Reads

NBS1 rs2735383 polymorphism is associated with an increased risk of laryngeal carcinoma.

BMC Cancer 2018 02 12;18(1):175. Epub 2018 Feb 12.

School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.

Background: Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability. Although single nucleotide polymorphisms (SNPs) in NBS1 have frequently been studied in multiple cancers, the relationships of two functional NBS1 polymorphisms (rs2735383 and rs1805794) with laryngeal carcinoma are yet unclear. Therefore, in the present study, we performed a case-control study including 342 cases and 345 controls to analyze the associations between two polymorphisms of NBS1 and the risk of laryngeal carcinoma. Read More

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http://dx.doi.org/10.1186/s12885-018-4078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810033PMC
February 2018
3 Reads

A non-synonymous polymorphism in is associated with progression from chronic hepatitis B virus infection to hepatocellular carcinoma in a Chinese population.

Onco Targets Ther 2018 26;11:563-569. Epub 2018 Jan 26.

Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan.

Purpose: Nijmegen breakage syndrome 1 (NBS1) has a vital role in DNA double-strand break (DSB) repair, functioning as a sensor to identify and repair DNA damage and maintaining genomic stability by participating in the intra-S-phase checkpoint. Polymorphisms of NBS1 have been investigated in multiple cancers with variable results. To our best knowledge, no previous study has focused on the association between single-nucleotide polymorphisms (SNPs) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Read More

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http://dx.doi.org/10.2147/OTT.S153538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790086PMC
January 2018
5 Reads

Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks.

Nat Cell Biol 2017 Dec 27;19(12):1400-1411. Epub 2017 Nov 27.

IFOM-The FIRC Institute of Molecular Oncology, Milan 20139, Italy.

The DNA damage response (DDR) preserves genomic integrity. Small non-coding RNAs termed DDRNAs are generated at DNA double-strand breaks (DSBs) and are critical for DDR activation. Here we show that active DDRNAs specifically localize to their damaged homologous genomic sites in a transcription-dependent manner. Read More

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http://dx.doi.org/10.1038/ncb3643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714282PMC
December 2017
12 Reads

Reversible Hypogammaglobulinemia in 2 Pediatric Patients With Primary Immunodeficiency.

Authors:
S Pasic

J Investig Allergol Clin Immunol 2017 ;27(5):320-321

Department of Pediatric Immunology, Mother and Child Health Institute, School of Medicine, University of Belgrade, Serbia.

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http://www.jiaci.org/summary/vol27-issue5-num1532
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http://dx.doi.org/10.18176/jiaci.0173DOI Listing
January 2017
1 Read

CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair.

Proc Natl Acad Sci U S A 2017 10 25;114(41):10912-10917. Epub 2017 Sep 25.

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;

CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). Read More

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http://dx.doi.org/10.1073/pnas.1704076114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642685PMC
October 2017
10 Reads

Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae.

Am J Med Genet A 2017 Nov 28;173(11):3075-3081. Epub 2017 Sep 28.

Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.

We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants-c.1523T>G, predicting (p. Read More

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http://dx.doi.org/10.1002/ajmg.a.38382DOI Listing
November 2017
6 Reads

MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress.

Cancer Res 2017 10 17;77(19):5327-5338. Epub 2017 Aug 17.

Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan.

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 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. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-17-1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831255PMC
October 2017
12 Reads

Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT).

Front Immunol 2017 24;8:807. Epub 2017 Jul 24.

Dmitry Rogachev National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Background: Nijmegen breakage syndrome (NBS) is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Read More

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http://journal.frontiersin.org/article/10.3389/fimmu.2017.00
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http://dx.doi.org/10.3389/fimmu.2017.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523727PMC
July 2017
15 Reads

Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.

Sci Rep 2017 Aug 8;7(1):7516. Epub 2017 Aug 8.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, 40225, Düsseldorf, Germany.

Nijmegen Breakage Syndrome (NBS) is associated with cancer predisposition, premature aging, immune deficiency, microcephaly and is caused by mutations in the gene coding for NIBRIN (NBN) which is involved in DNA damage repair. Dermal-derived fibroblasts from NBS patients were reprogrammed into induced pluripotent stem cells (iPSCs) in order to bypass premature senescence. The influence of antioxidants on intracellular levels of ROS and DNA damage were screened and it was found that EDHB-an activator of the hypoxia pathway, decreased DNA damage in the presence of high oxidative stress. Read More

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http://dx.doi.org/10.1038/s41598-017-07905-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548734PMC
August 2017
7 Reads

Effects of Pulsed Electromagnetic Fields on Breast Cancer Cell Line MCF 7 Using Absorption Spectroscopy.

Anticancer Res 2017 07;37(7):3453-3459

Faculty of Science, Liverpool Hope University, Liverpool, U.K.

We present an analysis of the effects of pulsed electromagnetic fields (PEMF) with 3.3 MHz carrier frequency and modulated by audio resonant frequencies on the MCF-7 breast cancer cell line in vitro using absorption spectroscopy. This involves a fluorescence dye called PrestoBlue™ Cell Viability Reagent and a spectrophotometry to test the viability of MCF-7 breast cancer cells under different PEMF treatment conditions in terms of the cell absorption values. Read More

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http://ar.iiarjournals.org/content/37/7/3453.abstract
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http://dx.doi.org/10.21873/anticanres.11713DOI Listing
July 2017
8 Reads

Cancer predisposition syndromes associated with myeloid malignancy.

Semin Hematol 2017 04 7;54(2):115-122. Epub 2017 Apr 7.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN. Electronic address:

The majority of myeloid malignancies are caused by sporadic somatic events rather than cancer predisposition. Nonetheless, the identification of hereditary cancer predisposition syndromes is critical when caring for patients with myeloid malignancies since detection may direct decisions related to cancer treatment and surveillance. A positive genetic test result also has important implications for other family members who can use this information to undergo their own testing to determine their cancer risk. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00371963173004
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http://dx.doi.org/10.1053/j.seminhematol.2017.04.003DOI Listing
April 2017
2 Reads

Hsp90α regulates ATM and NBN functions in sensing and repair of DNA double-strand breaks.

FEBS J 2017 08 9;284(15):2378-2395. Epub 2017 Jul 9.

Department of Sciences, Roma Tre University, Roma, Italy.

The molecular chaperone heat shock protein 90 (Hsp90α) regulates cell proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Read More

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http://dx.doi.org/10.1111/febs.14145DOI Listing
August 2017
17 Reads

Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders.

Clin Cancer Res 2017 Jun;23(11):e23-e31

National Cancer Institute, Rockville, Maryland.

DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. The majority of these syndromes are inherited in an autosomal-recessive manner, but autosomal-dominant and X-linked recessive disorders also exist. The clinical features of patients with DNA repair syndromes are highly varied and dependent on the underlying genetic cause. Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-17-0465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697784PMC
June 2017
41 Reads

DNA Damage Response in Human Stem Cells and Neural Descendants.

Methods Mol Biol 2017 ;1599:375-390

Department of Radiation Oncology and the Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Richmond, VA, 23298-0058, USA.

Glial cells are crucial for the normal function of neurons and are intricately involved in the pathogenesis of neurodegenerative diseases as well as neurologic malignancies. A deeper understanding of the mechanisms by which glial cells influence the development of such pathologies will undoubtedly lead to new and improved therapeutic approaches. Commercially available human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), both of which can be differentiated into neural progenitors (NPs) and various neural cell lineages, have become widely used as sources for producing normal human central nervous system (CNS) cells. Read More

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http://dx.doi.org/10.1007/978-1-4939-6955-5_27DOI Listing
February 2018
17 Reads

Contribution of Double-strand Break Repair Gene Nijmegen Breakage Syndrome 1 Genotypes, Gender Difference and Smoking Status to Taiwanese Lung Cancer.

Anticancer Res 2017 05;37(5):2417-2423

Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Background/aim: Nijmegen breakage syndrome 1 (NBS1) is a component of MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and maintenance of chromosomal integrity. Failure in DNA damage response affects the level of cell survival, increases the frequency of gene mutation or chromosomal instability and other cellular phenotypic abnormalities, which are the important mechanisms of carcinogenesis. However, the contribution of variant NBS1 genotypes to lung cancer is not known. Read More

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http://dx.doi.org/10.21873/anticanres.11581DOI Listing
May 2017
15 Reads

Parkin regulates translesion DNA synthesis in response to UV radiation.

Oncotarget 2017 May;8(22):36423-36437

State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. Read More

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http://dx.doi.org/10.18632/oncotarget.16855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482665PMC
May 2017
11 Reads

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.

J Allergy Clin Immunol 2018 Jan 7;141(1):322-328.e10. Epub 2017 Apr 7.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address:

Background: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). Read More

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http://dx.doi.org/10.1016/j.jaci.2017.02.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632132PMC
January 2018
54 Reads

NBS1 is regulated by two kind of mechanisms: ATM-dependent complex formation with MRE11 and RAD50, and cell cycle-dependent degradation of protein.

J Radiat Res 2017 Jul;58(4):487-494

Laboratory of Stress Response Biology, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8501, Japan.

Nijmegen breakage syndrome (NBS), a condition similar to Ataxia-Telangiectasia (A-T), is a radiation-hypersensitive genetic disorder showing chromosomal instability, radio-resistant DNA synthesis, immunodeficiency, and predisposition to malignances. The product of the responsible gene, NBS1, forms a complex with MRE11 and RAD50 (MRN complex). The MRN complex is necessary for the DNA damage-induced activation of ATM. Read More

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http://dx.doi.org/10.1093/jrr/rrx014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570008PMC
July 2017
10 Reads

Stimulation of lactate receptor (HCAR1) affects cellular DNA repair capacity.

DNA Repair (Amst) 2017 04 20;52:49-58. Epub 2017 Feb 20.

Department of Molecular Cell Mechanisms, Medical University of Lodz, Poland.

Numerous G-protein coupled receptors have been reported to enhance cancer cell survival and resistance to clinically used chemotherapeutics. Recently, hydroxycarboxylic acid receptor 1 (HCAR1) was shown to drive lactate-dependent enhancement of cell survival and metastasis in pancreatic and breast cancers. Furthermore, our previous study confirmed the involvement of HCAR1 in lactate-related enhancement of DNA repair in cervical cancer cells. Read More

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http://dx.doi.org/10.1016/j.dnarep.2017.02.007DOI Listing
April 2017
3 Reads

NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres.

Mol Cell 2017 Mar 16;65(5):801-817.e4. Epub 2017 Feb 16.

Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA; Molecular Biophysics and Biochemistry, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA. Electronic address:

Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. Read More

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http://dx.doi.org/10.1016/j.molcel.2017.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639704PMC
March 2017
8 Reads

Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene.

BMC Cancer 2017 02 10;17(1):119. Epub 2017 Feb 10.

Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Cernopolni 9, Brno, 613 00, Czech Republic.

Background: Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known, namely in tumors with visceral involvement. The standard of care is surgical resection. Read More

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http://dx.doi.org/10.1186/s12885-017-3115-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301362PMC
February 2017
18 Reads

An Approach to Elucidate NBS1 Function in DNA Repair Using Frequent Nonsynonymous Polymorphism in Wild Medaka (Oryzias latipes) Populations.

PLoS One 2017 20;12(1):e0170006. Epub 2017 Jan 20.

Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.

Nbs1 is one of the genes responsible for Nijmegen breakage syndrome, which is marked with high radiosensitivity. In human NBS1 (hNBS1), Q185E polymorphism is known as the factor to cancer risks, although its DSB repair defect has not been addressed. Here we investigated the genetic variations in medaka (Oryzias latipes) wild populations, and found 40 nonsynonymous single nucleotide polymorphisms (SNPs) in medaka nbs1 (olnbs1) gene within 5 inbred strains. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170006PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249114PMC
August 2017
3 Reads

The Mre11-Nbs1 Interface Is Essential for Viability and Tumor Suppression.

Cell Rep 2017 01;18(2):496-507

Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. Electronic address:

The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling. All three Mre11 complex components are essential for viability at the cellular and organismal levels. To delineate essential and non-essential Mre11 complex functions that are mediated by Nbs1, we used TALEN-based genome editing to derive Nbs1 mutant mice (Nbs1 mice), which harbor mutations in the Mre11 interaction domain of Nbs1. Read More

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http://dx.doi.org/10.1016/j.celrep.2016.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234850PMC
January 2017
3 Reads

Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome.

Redox Biol 2017 04 28;11:375-383. Epub 2016 Dec 28.

Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37 Str., 15-295 Bialystok, Poland. Electronic address:

Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Read More

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http://dx.doi.org/10.1016/j.redox.2016.12.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219618PMC
April 2017
6 Reads

Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.

J Clin Immunol 2017 Feb 21;37(2):133-142. Epub 2016 Dec 21.

Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.

Purpose: The Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence. Read More

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http://dx.doi.org/10.1007/s10875-016-0363-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325864PMC
February 2017
11 Reads

The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?

PLoS One 2016 9;11(12):e0167984. Epub 2016 Dec 9.

Cologne Center for Genomics, University of Cologne, Köln, Germany.

The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167984PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148078PMC
July 2017
13 Reads

Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer.

Fam Cancer 2017 07;16(3):389-394

Department of Pathology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110, Safat, Kuwait.

Nijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation in NBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers of NBN gene are also reported to be at increased risk of developing various types of malignancy. Read More

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http://dx.doi.org/10.1007/s10689-016-9954-9DOI Listing
July 2017
50 Reads
1.620 Impact Factor

High Expression of MRE11-RAD50-NBS1 Is Associated with Poor Prognosis and Chemoresistance in Gastric Cancer.

Anticancer Res 2016 10;36(10):5237-5247

Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.

Background: The MRN complex of meiotic recombination 11 (MRE11), DNA repair protein Rad50 (RAD50) and Nijmegen breakage syndrome 1 (NBS1) proteins coordinate the detection and repair of DNA double-strand breaks (DSBs). DNA DSB repair-dependent chemoresistance likely has an effect on the treatment of human cancer.

Materials And Methods: We investigated the expression of MRN complex in human gastric cancer (GC) tissues using immunohistochemistry and analyzed its clinical significance and prognostic relevance. Read More

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http://dx.doi.org/10.21873/anticanres.11094DOI Listing
October 2016
13 Reads

T-lymphoblastic leukemia/lymphoma in macedonian patients with Nijmegen breakage syndrome.

Balkan J Med Genet 2016 Jul 2;19(1):91-94. Epub 2016 Aug 2.

Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, University "St. Cyril and Methodius," Skopje, Republic of Macedonia.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability disorder characterized by microcephaly, immunodeficiency, radiosensitivity and a very high predisposition to malignancy. The gene responsible for the disease, , is located on chromosome 8q21 and encodes a protein called nibrin. After identification of the gene, a truncating 5 bp deletion, 657-661delACAAA, was identified as the disease-causing mutation in patients with the NBS. Read More

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http://content.sciendo.com/view/journals/bjmg/19/1/article-p
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http://dx.doi.org/10.1515/bjmg-2016-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026285PMC
July 2016
2 Reads

Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients.

Cell Rep 2016 08 18;16(9):2499-511. Epub 2016 Aug 18.

Department of Genetics, Institute of Life Sciences, The Hebrew University, Givat-Ram, Jerusalem 91904, Israel. Electronic address:

Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here, we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Read More

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http://dx.doi.org/10.1016/j.celrep.2016.07.071DOI Listing
August 2016
8 Reads

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents.

Haematologica 2016 12 11;101(12):1581-1591. Epub 2016 Aug 11.

Pediatric Hematology and Oncology, University of Padova, Italy.

Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. Read More

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http://dx.doi.org/10.3324/haematol.2016.147116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479624PMC
December 2016
28 Reads
1 Citation
5.870 Impact Factor

NBS1 and multiple regulations of DNA damage response.

Authors:
Kenshi Komatsu

J Radiat Res 2016 Aug 10;57 Suppl 1:i11-i17. Epub 2016 Apr 10.

Division of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Sakyo-Ku, Kyoto 606-8501, Japan

DNA damage response is finely tuned, with several pathways including those for DNA repair, chromatin remodeling and cell cycle checkpoint, although most studies to date have focused on single pathways. Genetic diseases characterized by genome instability have provided novel insights into the underlying mechanisms of DNA damage response. NBS1, a protein responsible for the radiation-sensitive autosomal recessive disorder Nijmegen breakage syndrome, is one of the first factors to accumulate at sites of DNA double-strand breaks (DSBs). Read More

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http://dx.doi.org/10.1093/jrr/rrw031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990113PMC
August 2016
3 Reads

Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis.

Oncotarget 2016 Apr;7(17):23006-18

Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. Read More

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http://dx.doi.org/10.18632/oncotarget.8470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029606PMC
April 2016
9 Reads

The MRX Complex Ensures NHEJ Fidelity through Multiple Pathways Including Xrs2-FHA-Dependent Tel1 Activation.

PLoS Genet 2016 Mar 18;12(3):e1005942. Epub 2016 Mar 18.

Department of Integrated Protein Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.

Because DNA double-strand breaks (DSBs) are one of the most cytotoxic DNA lesions and often cause genomic instability, precise repair of DSBs is vital for the maintenance of genomic stability. Xrs2/Nbs1 is a multi-functional regulatory subunit of the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex, and its function is critical for the primary step of DSB repair, whether by homologous recombination (HR) or non-homologous end joining. In human NBS1, mutations result truncation of the N-terminus region, which contains a forkhead-associated (FHA) domain, cause Nijmegen breakage syndrome. Read More

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http://dx.plos.org/10.1371/journal.pgen.1005942
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http://dx.doi.org/10.1371/journal.pgen.1005942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798412PMC
March 2016
12 Reads

Generation of iPSC lines from a Nijmegen Breakage Syndrome patient.

Stem Cell Res 2015 Nov 23;15(3):629-32. Epub 2015 Oct 23.

Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany; Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany. Electronic address:

Human dermal fibroblasts from a Nijmegen Breakage Syndrome (NBS) patient bearing the 657del5 mutation within the DNA repair gene NIBRIN were used to generate two iPSC-lines (vNBS8-iPS-c1, vNBS8-iPS-c2) by retroviral transduction of OCT4, SOX2, c-MYC and KLF4. Pluripotency was confirmed both in vivo and in vitro. Read More

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http://dx.doi.org/10.1016/j.scr.2015.10.013DOI Listing
November 2015
2 Reads

Severe mitochondrial damage associated with low-dose radiation sensitivity in ATM- and NBS1-deficient cells.

Cell Cycle 2016 ;15(8):1099-107

a Department of Environmental Health , National Institute of Public Health , Wako , Saitama , Japan.

Low-dose radiation risks remain unclear owing to a lack of sufficient studies. We previously reported that low-dose, long-term fractionated radiation (FR) with 0.01 or 0. Read More

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http://dx.doi.org/10.1080/15384101.2016.1156276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889229PMC
January 2017
12 Reads