662 results match your criteria Nijmegen Breakage Syndrome


E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair.

Nat Commun 2019 10 30;10(1):4951. Epub 2019 Oct 30.

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX, 78957, USA.

E2F1 and retinoblastoma (RB) tumor-suppressor protein not only regulate the periodic expression of genes important for cell proliferation, but also localize to DNA double-strand breaks (DSBs) to promote repair. E2F1 is acetylated in response to DNA damage but the role this plays in DNA repair is unknown. Here we demonstrate that E2F1 acetylation creates a binding motif for the bromodomains of the p300/KAT3B and CBP/KAT3A acetyltransferases and that this interaction is required for the recruitment of p300 and CBP to DSBs and the induction of histone acetylation at sites of damage. Read More

View Article and Full-Text PDF
October 2019

Antioxidant Defense, Redox Homeostasis, and Oxidative Damage in Children With Ataxia Telangiectasia and Nijmegen Breakage Syndrome.

Front Immunol 2019 27;10:2322. Epub 2019 Sep 27.

Department of Pediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok, Poland.

Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Read More

View Article and Full-Text PDF
November 2020

Chromosome instability syndromes.

Nat Rev Dis Primers 2019 09 19;5(1):64. Epub 2019 Sep 19.

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Fanconi anaemia (FA), ataxia telangiectasia (A-T), Nijmegen breakage syndrome (NBS) and Bloom syndrome (BS) are clinically distinct, chromosome instability (or breakage) disorders. Each disorder has its own pattern of chromosomal damage, with cells from these patients being hypersensitive to particular genotoxic drugs, indicating that the underlying defect in each case is likely to be different. In addition, each syndrome shows a predisposition to cancer. Read More

View Article and Full-Text PDF
September 2019

Nbn-Mre11 interaction is required for tumor suppression and genomic integrity.

Proc Natl Acad Sci U S A 2019 07 8;116(30):15178-15183. Epub 2019 Jul 8.

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

We derived a mouse model in which a mutant form of Nbn/Nbs1 (hereafter Nbn) exhibits severely impaired binding to the Mre11-Rad50 core of the Mre11 complex. The allele was expressed exclusively in hematopoietic lineages (in mice). Unlike mice with Nbn deficiency in the bone marrow, mice were viable. Read More

View Article and Full-Text PDF

Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration.

Brain Commun 2019 2;1(1):fcz005. Epub 2019 Jul 2.

Neuroscience and Ophthalmology, College of Medical and Dental Sciences, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Read More

View Article and Full-Text PDF

A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management.

Gynecol Endocrinol 2019 Nov 12;35(11):999-1002. Epub 2019 Jun 12.

Department of Gynecological Endocrinology, Poznan University of Medical Sciences , Poznan , Poland.

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS. Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed. Read More

View Article and Full-Text PDF
November 2019

Two novel variants in the ATM gene causing ataxia-telangiectasia, including a duplication of 90 kb: Utility of targeted next-generation sequencing in detection of copy number variation.

Ann Hum Genet 2019 07 19;83(4):266-273. Epub 2019 Mar 19.

Department of Biomedical Diagnostics, Hospital San Pedro, Logroño, Spain.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, ocular apraxia, immunodeficiency, telangiectasia, elevated serum α-fetoprotein concentration, radiosensitivity and cancer predisposition. Classical A-T is caused by biallelic variants on ATM (ataxia telangiectasia mutated) gene, leading to a loss of function of the protein kinase ATM, involved in DNA damage repair. Atypical presentations can be found in A-T-like disease or in Nijmegen breakage syndrome, caused by deficiency of mre11 or nibrin proteins, respectively. Read More

View Article and Full-Text PDF

Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population.

Technol Cancer Res Treat 2018 01;17:1533033818819841

1 Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Objective: The aim of the study was to estimate breast cancer risk conferred by individual single-nucleotide polymorphisms of breast cancer susceptibility genes.

Methods: We analyzed the 48 tagging single-nucleotide polymorphisms of 8 breast cancer susceptibility genes involved in the monoubiquitinated FANCD2-DNA damage repair pathway in 734 Chinese women with breast cancer and 672 age-matched healthy controls.

Results: Forty-five tagging single-nucleotide polymorphisms were successfully genotyped by SNPscan, and the call rates for each tagging single-nucleotide polymorphisms were above 98. Read More

View Article and Full-Text PDF
January 2018

Fibroblast-derived integration-free iPSC line ISRM-NBS1 from an 18-year-old Nijmegen Breakage Syndrome patient carrying the homozygous NBN c.657_661del5 mutation.

Stem Cell Res 2019 01 27;34:101372. Epub 2018 Dec 27.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address:

Human fibroblasts cells from a female diagnosed with Nijmegen Breakage Syndrome (NBS) carrying the homozygous NBN c.657_661del5 mutation were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, KLF4, c-MYC and LIN28. The derived iPSC line - ISRM-NBS1 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0. Read More

View Article and Full-Text PDF
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 01 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

View Article and Full-Text PDF
January 2019

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

View Article and Full-Text PDF
November 2018

Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.

Pediatrics 2018 10 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

View Article and Full-Text PDF
October 2018

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.

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

Annu Rev Biochem 2018 06 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

View Article and Full-Text PDF

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

Eur J Hum Genet 2018 09 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

View Article and Full-Text PDF
September 2018

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

Am J Med Genet A 2018 06 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

View Article and Full-Text PDF

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

View Article and Full-Text PDF

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

Cancer 2018 08 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

View Article and Full-Text PDF

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

View Article and Full-Text PDF
October 2018

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

View Article and Full-Text PDF
February 2018

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

View Article and Full-Text PDF
February 2018

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

View Article and Full-Text PDF
January 2018

Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2-MRN-ATM axes.

Cell Death Dis 2018 02 2;9(2):145. Epub 2018 Feb 2.

Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal protein and a direct p53 target. We recently reported that Rps27l disruption triggers ribosomal stress to induce p53, causing postnatal death, which can be rescued by Trp53 . Whether and how Rps27l modulates radiosensitivity is unknown. Read More

View Article and Full-Text PDF
February 2018

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

View Article and Full-Text PDF
December 2017

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.

View Article and Full-Text PDF