676 results match your criteria Nijmegen Breakage Syndrome

Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations.

Klin Onkol 2022 ;35(2):119-127

Background: Ionizing radiation DNA damage is the main mechanism of radiotherapy (RT) action and the outcome of treatment and healthy tissue toxicity is influenced by a number of external and internal factors, including mutations in DNA damage recognition and repair. Disorders of DNA repair may result in increased sensitivity to cancer treatment.

Purpose: The mechanism of DNA repair and an overview of genetic syndromes with mutations in genes involved in DNA repair clarify the accelerated carcinogenesis and increased radiosensitivity in RT cancers. Read More

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Consensus Recommendations for the Clinical Management of Hematological Malignancies in Patients with DNA Double Stranded Break Disorders.

Cancers (Basel) 2022 Apr 14;14(8). Epub 2022 Apr 14.

Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Patients with double stranded DNA repair disorders (DNARDs) (Ataxia Telangiectasia (AT) and Nijmegen Breakage syndrome (NBS)) are at a very high risk for developing hematological malignancies in the first two decades of life. The most common neoplasms are T-cell lymphoblastic malignancies (T-cell ALL and T-cell LBL) and diffuse large B cell lymphoma (DLBCL). Treatment of these patients is challenging due to severe complications of the repair disorder itself (e. Read More

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NBS1 protein from Physcomitrium patens confers protection against oxidative damage by limiting the accumulation of cellular reactive oxygen species.

Plant Physiol Biochem 2022 Apr 5;180:81-90. Epub 2022 Apr 5.

Plant Functional Genomics Laboratory, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, West Bengal, India. Electronic address:

Nijmegen breakage syndrome 1 (NBS1) protein is a core member of the MRE11-RAD50-NBS1 (MRN) complex that plays a crucial role in DNA damage sensing and repair in plants. Here we report that NBS1 from moss Physcomitrium patens reduces oxidative damage by lowering the cellular ROS in addition to its known role in oxidative DNA damage recovery. Real-time transcript analysis showed up-regulation of the PpNBS1 transcript under different stress conditions. Read More

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Impaired p53-Mediated DNA Damage Response Contributes to Microcephaly in Nijmegen Breakage Syndrome Patient-Derived Cerebral Organoids.

Cells 2022 02 25;11(5). Epub 2022 Feb 25.

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

Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder caused by mutations within nibrin (), a DNA damage repair protein. Hallmarks of NBS include chromosomal instability and clinical manifestations such as growth retardation, immunodeficiency, and progressive microcephaly. We employed induced pluripotent stem cell-derived cerebral organoids from two NBS patients to study the etiology of microcephaly. Read More

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February 2022

Subcutaneous injection of infliximab CT-P13 results in stable drug levels within 14-day treatment cycle in Crohn's disease.

Aliment Pharmacol Ther 2022 07 28;56(1):77-83. Epub 2022 Feb 28.

CIRI (Centre International de Recherche en Infectiologie), Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, France.

The new subcutaneous (sc) formulation of the infliximab (IFX) biosimilar CT-P13 results in homogeneous serum trough concentrations of IFX at steady state. The present study aimed to investigate in Crohn's disease (CD) patients the intra-individual variations of IFX drug levels at multiple time-points during 2 consecutive cycles of maintenance therapy with CT-P13 sc.

Patients And Methods: CD patients in clinico-biological remission under maintenance therapy with intravenous (iv) IFX/CT-P13 were switched to CT-P13 sc 8 weeks (W) after the last infusion. Read More

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NBS1-CtIP-mediated DNA end resection suppresses cGAS binding to micronuclei.

Nucleic Acids Res 2022 03;50(5):2681-2699

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is activated in cells with defective DNA damage repair and signaling (DDR) factors, but a direct role for DDR factors in regulating cGAS activation in response to micronuclear DNA is still poorly understood. Here, we provide novel evidence that Nijmegen breakage syndrome 1 (NBS1) protein, a well-studied DNA double-strand break (DSB) sensor-in coordination with Ataxia Telangiectasia Mutated (ATM), a protein kinase, and Carboxy-terminal binding protein 1 interacting protein (CtIP), a DNA end resection factor-functions as an upstream regulator that prevents cGAS from binding micronuclear DNA. When NBS1 binds to micronuclear DNA via its fork-head-associated domain, it recruits CtIP and ATM via its N- and C-terminal domains, respectively. Read More

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The Essential DNA Damage Response Complex MRN Is Dispensable for the Survival and Function of Purkinje Neurons.

Front Aging Neurosci 2021 28;13:786199. Epub 2022 Jan 28.

School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.

MRE11, RAD50, and NBS1 form the MRN complex in response to DNA damage to activate ATM, a gene responsible for Ataxia-Telangiectasia (A-T). Loss of any components of the MRN complex compromises cell life. Mutations in , , and cause human genomic instability syndromes Ataxia-Telangiectasia-like disorder (A-TLD), NBS-like disorder (NBSLD), and Nijmegen Breakage Syndrome (NBS), respectively. Read More

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January 2022

An analysis to identify structural, functional and regulatory role of SNPs in .

J Biomol Struct Dyn 2022 Jan 20:1-15. Epub 2022 Jan 20.

Department of Cancer Biology, Stem Cell Biology Lab, The Gujarat Cancer and Research Institute, Ahmedabad, India.

Meiotic recombination 11 () is a component of the tri-molecular -RAD50-NBS1 (MRN) complex, which functions as an exonuclease and endonuclease which is involved in identifying, signalling, protecting and repairing double-strand breaks in DNA (DSBs). Ataxia-telangiectasia-like disorder (ATLD) 1 and Nijmegen breakage syndrome (NBS)-like disorder are associated diseases. In the present study, we used an integrated computational approach to identify the most deleterious SNPs and their structural and functional impact on human . Read More

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January 2022

GSTpi reduces DNA damage and cell death by regulating the ubiquitination and nuclear translocation of NBS1.

Cell Mol Life Sci 2021 Dec 22;79(1):54. Epub 2021 Dec 22.

Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, No.1 Wenyuan Road, Nanjing, 210046, People's Republic of China.

Glutathione S-transferase pi (GSTpi) is an important phase II detoxifying enzyme that participates in various physiological processes, such as antioxidant, detoxification, and signal transduction. The high expression level of GSTpi has been reported to be related to drug-resistant and anti-inflammatory and it functioned via its non-catalytic ligandin. However, the previous protection mechanism of GSTpi in DNA damage has not been addressed so far. Read More

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December 2021

Bilateral Ovarian Germ Cell Tumor in a 46,XX Female with Nijmegen Breakage Syndrome and Hypergonadotropic Hypogonadism

J Clin Res Pediatr Endocrinol 2022 06 21;14(2):251-257. Epub 2021 Sep 21.

Medical University of Gdansk, Department of Pediatrics, Hematology and Oncology, Gdansk, Poland

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, affecting mainly patients of Slavic origin. It is caused by a defect in the gene, resulting in defective nibrin protein formation. This leads to chromosomal instability, which predisposes to cancer, with lymphoid malignancies predominating. Read More

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Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes.

Am J Hematol 2021 11 27;96(11):1450-1460. Epub 2021 Aug 27.

Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Read More

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November 2021

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells.

Int J Mol Sci 2021 Jul 26;22(15). Epub 2021 Jul 26.

School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea.

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Read More

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MRN Complex and Cancer Risk: Old Bottles, New Wine.

Clin Cancer Res 2021 10 14;27(20):5465-5471. Epub 2021 Jul 14.

Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.

The MRN complex, composed of MRE11A, RAD50, and NBN, mediates vital molecular functions to maintain genomic stability and hence protect against related disorders. Germline mutations in the MRN genes predispose to three different syndromes: ataxia-telangiectasia-like disorder (MRE11A deficiency), Nijmegen breakage syndrome (NBS; NBN deficiency), and NBS-like disorder (RAD50 deficiency). The potential cancer component of these syndromes in addition to the close physical and functional proximity of the MRN complex to BRCA1 has promoted the MRN genes as candidate risk genes for developing breast cancer. Read More

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October 2021

Editorial: Advances in Primary Immunodeficiency in Central-Eastern Europe.

Front Immunol 2021 14;12:667727. Epub 2021 May 14.

Primary Immunodeficiency Clinical Unit and Laboratory, Department of Dermatology, Venerology, and Dermatooncology, Semmelweis University, Budapest, Hungary.

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October 2021

MYC/NBS1-Mediated DNA Damage Response is Involved in the Inhibitory Effect of Hydroxysafflor Yellow A on Glioma Cells.

Drug Des Devel Ther 2021 28;15:1749-1763. Epub 2021 Apr 28.

Department of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an City, People's Republic of China.

Background: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells.

Methods: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. Read More

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November 2021

Nbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.

Cell Prolif 2021 Mar 14;54(3):e12972. Epub 2021 Feb 14.

Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, China.

Objectives: DNA damages pose threats to haematopoietic stem cells (HSC) maintenance and haematopoietic system homeostasis. Quiescent HSCs in adult mouse bone marrow are resistant to DNA damage, while human umbilical cord blood-derived proliferative HSCs are prone to cell death upon ionizing radiation. Murine embryonic HSCs proliferate in foetal livers and divide symmetrically to generate HSC pool. Read More

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Impairment of sirtuin 1-mediated DNA repair is involved in bisphenol A-induced aggravation of macrophage inflammation and atherosclerosis.

Chemosphere 2021 Feb 18;265:128997. Epub 2020 Nov 18.

Institute of Cardiovascular Diseases of PLA & Department of Cardiology, The Second Affiliated Hospital, Army Medical University, Chongqing, China. Electronic address:

Bisphenol A (BPA), an environmental pollutant, has received considerable attention worldwide for its hazardous effects of promoting atherosclerosis and increasing the risk of cardiovascular diseases (CVDs). However, the mechanisms involved are unclear. We aimed to investigate the mechanisms underlying BPA-aggravated atherosclerosis and potential preventive treatments. Read More

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February 2021

DNA Repair Syndromes and Cancer: Insights Into Genetics and Phenotype Patterns.

Front Pediatr 2020 23;8:570084. Epub 2020 Oct 23.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, United States.

DNA damage response is essential to human physiology. A broad spectrum of pathologies are displayed by individuals carrying monoallelic or biallelic loss-of-function mutations in DNA damage repair genes. DNA repair syndromes with biallelic disturbance of essential DNA damage response pathways manifest early in life with multi-systemic involvement and a high propensity for hematologic and solid cancers, as well as bone marrow failure. Read More

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October 2020

Newborn Screening for SCID and Other Severe Primary Immunodeficiency in the Polish-German Transborder Area: Experience From the First 14 Months of Collaboration.

Front Immunol 2020 16;11:1948. Epub 2020 Oct 16.

Department of Immunology, The Children's Memorial Health Institute, Warsaw, Poland.

In 2017, in the Polish-German transborder area of West Pomerania, Mecklenburg-Western Pomerania, and Brandenburg, in collaboration with two centers in Warsaw, a partnership in the field of newborn screening (NBS) for severe primary immunodeficiency diseases (PID), mainly severe combined immunodeficiency (SCID), was initiated. SCID, but also some other severe PID, is a group of disorders characterized by the absence of T and/or B and NK cells. Affected infants are susceptible to life-threatening infections, but early detection gives a chance for effective treatment. Read More

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Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome.

Clin Cancer Res 2021 01 20;27(2):575-584. Epub 2020 Oct 20.

Research Unit Pediatric Hematology and Immunology, Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies.

Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency.

Results: Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63. Read More

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January 2021

ROS-dependent DNA damage and repair during germination of NaCl primed seeds.

J Photochem Photobiol B 2020 Dec 10;213:112050. Epub 2020 Oct 10.

Department of Plant Sciences, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India. Electronic address:

Reactive oxygen species (ROS) generated during rehydration of seeds is a major source of cellular damage. Successful germination depends on maintaining the oxidative window and ability of the cells to repair the DNA damage accumulated during seed developmental process, maturational drying, and germination. We explored the role of DNA damage, repair, cell cycle progression and antioxidant machinery in germination of seeds of Solanum melongena L. Read More

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December 2020

NBS1 interacts with Notch signaling in neuronal homeostasis.

Nucleic Acids Res 2020 11;48(19):10924-10939

Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.

NBS1 is a critical component of the MRN (MRE11/RAD50/NBS1) complex, which regulates ATM- and ATR-mediated DNA damage response (DDR) pathways. Mutations in NBS1 cause the human genomic instability syndrome Nijmegen Breakage Syndrome (NBS), of which neuronal deficits, including microcephaly and intellectual disability, are classical hallmarks. Given its function in the DDR to ensure proper proliferation and prevent death of replicating cells, NBS1 is essential for life. Read More

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November 2020

Hepatitis B virus preS2Δ38-55 variants: A newly identified risk factor for hepatocellular carcinoma.

JHEP Rep 2020 Oct 11;2(5):100144. Epub 2020 Jul 11.

INSERM U1052, CNRS 5286, Univ Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.

Background & Aims: Although HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia.

Methods: We conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Read More

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October 2020

Chromosomal instability associated with adverse outcome: a case report of patient with Nijmegen breakage syndrome and rapidly developed T-NHL with complex karyotype.

Mol Cytogenet 2020 20;13:35. Epub 2020 Aug 20.

Laboratory of Genetic Diagnostics, Medical University of Lublin, Lublin, Poland.

Background: Nijmegen breakage syndrome (NBS) is a rare genetic disorder inherited in an autosomal recessive pattern associated with an increased risk of developing lymphoproliferative disorders, mainly non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). NBS patients are 50 times more likely to develop malignancy than healthy controls. Moreover, in NBS, mortality rate from cancers, mainly lymphomas, is the highest among all diseases associated with excessive fragility of chromosomes. Read More

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T Lymphocytes in Patients With Nijmegen Breakage Syndrome Demonstrate Features of Exhaustion and Senescence in Flow Cytometric Evaluation of Maturation Pathway.

Front Immunol 2020 30;11:1319. Epub 2020 Jun 30.

Department of Microbiology and Clinical Immunology, Children's Memorial Health Institute, Warsaw, Poland.

Patients with Nijmegen Breakage Syndrome (NBS) suffer from recurrent infections due to humoral and cellular immune deficiency. Despite low number of T lymphocytes and their maturation defect, the clinical manifestations of cell-mediated deficiency are not as severe as in case of patients with other types of combined immune deficiencies and similar T cell lymphopenia. In this study, multicolor flow cytometry was used for evaluation of peripheral T lymphocyte maturation according to the currently known differentiation pathway, in 46 patients with genetically confirmed NBS and 46 sex and age-matched controls. Read More

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A Survey of Reported Disease-Related Mutations in the MRE11-RAD50-NBS1 Complex.

Cells 2020 07 13;9(7). Epub 2020 Jul 13.

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.

The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaining proper cellular function. Mutations in any one of the components of the MRN complex that effect function or expression of the repair machinery could be detrimental to the cell and may initiate and/or propagate disease. Read More

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Update on DNA-Double Strand Break Repair Defects in Combined Primary Immunodeficiency.

Curr Allergy Asthma Rep 2020 07 9;20(10):57. Epub 2020 Jul 9.

Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Great North Children's Hospital, Clinical Resource Building, Floor 4, Block 2, Newcastle upon Tyne, UK.

Purpose Of Review: The most serious DNA damage, DNA double strand breaks (DNA-dsb), leads to mutagenesis, carcinogenesis or apoptosis if left unrepaired. Non-homologous end joining (NHEJ) is the principle repair pathway employed by mammalian cells to repair DNA-dsb. Several proteins are involved in this pathway, defects in which can lead to human disease. Read More

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Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome.

J Clin Immunol 2020 08 30;40(6):861-871. Epub 2020 Jun 30.

Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela str, Moscow, Russia, 117997.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150 mg/m, cyclophosphamide 20-40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Read More

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Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome.

Aging (Albany NY) 2020 06 20;12(12):12342-12375. Epub 2020 Jun 20.

Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Rostock, Germany.

Background: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy.

Results: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Read More

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