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PMID:9590181

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Citation

Carney, JP, Maser, RS, Olivares, H, Davis, EM, Le Beau, M, Yates, JR 3rd, Hays, L, Morgan, WF and Petrini, JH (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93:477-86

Abstract

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by increased cancer incidence, cell cycle checkpoint defects, and ionizing radiation sensitivity. We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. The p95 gene mapped to 8q21.3, the region that contains the NBS locus, and p95 was absent from NBS cells established from NBS patients. p95 deficiency in these cells completely abrogates the formation of hMre11/hRad50 ionizing radiation-induced foci. Comparison of the p95 cDNA to the NBS1 cDNA indicated that the p95 gene and NBS1 are identical. The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions.

Links

PubMed

Keywords

Cell Cycle Proteins/analysis; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/genetics; Cell Cycle Proteins/isolation & purification; Cell Cycle Proteins/physiology; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 8/genetics; Cloning, Molecular; DNA Damage/genetics; DNA Repair/genetics; DNA Repair Enzymes; DNA, Complementary/genetics; DNA-Binding Proteins/analysis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Fibroblasts/radiation effects; Genes, Recessive/genetics; HeLa Cells; Humans; Microcephaly/genetics; Molecular Sequence Data; Molecular Weight; Nuclear Proteins; Proteins/analysis; Proteins/genetics; Proteins/metabolism; RNA, Messenger/analysis; Radiation Tolerance; Radiation, Ionizing; Sequence Homology, Amino Acid; Species Specificity; Syndrome

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