Linkage between Werner Syndrome Protein and the Mre11 Complex via Nbs1
| Autor: | Cayetano von Kobbe, Patricia L. Opresko, Vilhelm A. Bohr, Michael M. Seidman, Wen-Hsing Cheng, L. Matthew Arthur, Kenshi Komatsu, James P. Carney |
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| Rok vydání: | 2004 |
| Předmět: |
Premature aging
Genome instability congenital hereditary and neonatal diseases and abnormalities Small interfering RNA Werner Syndrome Helicase Mitomycin RecQ helicase Cell Cycle Proteins Biology Transfection Biochemistry Cell Line Mre11 complex Reference Values medicine Humans RNA Messenger Molecular Biology Werner syndrome Genetics MRE11 Homologue Protein Binding Sites RecQ Helicases DNA Helicases Nuclear Proteins nutritional and metabolic diseases Cell Biology medicine.disease Recombinant Proteins DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Exodeoxyribonucleases Gamma Rays Rad50 Nijmegen breakage syndrome HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 279:21169-21176 |
| ISSN: | 0021-9258 |
| Popis: | The Werner syndrome and the Nijmegen breakage syndrome are recessive genetic disorders that show increased genomic instability, cancer predisposition, hypersensitivity to mitomycin C and gamma-irradiation, shortened telomeres, and cell cycle defects. The protein mutated in the premature aging disease known as the Werner syndrome is designated WRN and is a member of the RecQ helicase family. The Nbs1 protein is mutated in Nijmegen breakage syndrome individuals and is part of the mammalian Mre11 complex together with the Mre11 and Rad50 proteins. Here, we show that WRN associates with the Mre11 complex via binding to Nbs1 in vitro and in vivo. In response to gamma-irradiation or mitomycin C, WRN leaves the nucleoli and co-localizes with the Mre11 complex in the nucleoplasm. We detect an increased association between WRN and the Mre11 complex after cellular exposure to gamma-irradiation. Small interfering RNA and complementation experiments demonstrated convergence of WRN and Nbs1 in response to gamma-irradiation or mitomycin C. Nbs1 is required for the Mre11 complex promotion of WRN helicase activity. Taken together, these results demonstrate a functional link between the two genetic diseases with partially overlapping phenotypes in a pathway that responds to DNA double strand breaks and interstrand cross-links. |
| Databáze: | OpenAIRE |
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