Nibrin, a Novel DNA Double-Strand Break Repair Protein, Is Mutated in Nijmegen Breakage Syndrome
نویسندگان
چکیده
Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Cells from NBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from ataxia telangiectasia. We describe the positional cloning of a gene encoding a novel protein, nibrin. It contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain. A truncating 5 bp deletion was identified in the majority of NBS patients, carrying a conserved marker haplotype. Five further truncating mutations were identified in patients with other distinct haplotypes. The domains found in nibrin and the NBS phenotype suggest that this disorder is caused by defective responses to DNA double-strand breaks.
منابع مشابه
Primary immunodeficiency syndromes associated with defective DNA double-strand break repair.
Damaging DNA double-strand breaks (DNA-DSBs) following ionizing radiation (IR) exposure, potentially lead to cell death or carcinogenesis. Non-homologous end-joining (NHEJ) is the main repair pathway employed by vertebrate cells to repair such damage. Many repair pathway proteins have been identified. The creation of many diverse lymphocyte receptors to identify potential pathogens has evolved ...
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Nijmegen Breakage Syndrome (NBS), an autosomal recessive genetic instability syndrome, is caused by hypomorphic mutation of the NBN gene, which codes for the protein nibrin. Nibrin is an integral member of the MRE11/RAD50/NBN (MRN) complex essential for processing DNA double-strand breaks. Cardinal features of NBS are immunodeficiency and an extremely high incidence of hematological malignancie...
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EDITOR—Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability disorder characterised by microcephaly, immunodeficiency, x ray hypersensitivity, and predisposition to malignancy. The gene responsible for NBS, NBS1, is located on chromosome 8q21 and encodes a protein called nibrin. This protein is a component of the hMre11/hRad50 protein complex, suggesting defecti...
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Nijmegen breakage syndrome is a rare autosomal recessive genetic disease belonging to a group of disorders often called chromosome instability syndromes. In addition to a characteristic facial appearance and microcephaly, patients suffering from Nijmegen breakage syndrome have a range of symptoms including radiosensitivity, immunodeficiency, increased cancer risk and growth retardation. The und...
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ورودعنوان ژورنال:
- Cell
دوره 93 شماره
صفحات -
تاریخ انتشار 1998