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- Anna M. Szekely
- Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510; and Department of Pathology, University of Washington, Seattle, WA 98195
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- Yao-Hui Chen
- Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510; and Department of Pathology, University of Washington, Seattle, WA 98195
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- Chunyu Zhang
- Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510; and Department of Pathology, University of Washington, Seattle, WA 98195
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- Junko Oshima
- Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510; and Department of Pathology, University of Washington, Seattle, WA 98195
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- Sherman M. Weissman
- Boyer Center for Molecular Medicine and Department of Genetics, Yale University School of Medicine, New Haven CT, 06510; and Department of Pathology, University of Washington, Seattle, WA 98195
抄録
<jats:p> Werner syndrome is a Mendelian disorder of man that produces a number of manifestations resembling human aging. This disorder is caused by inactivation of the <jats:italic>wrn</jats:italic> gene, a member of the RecQ family of DNA helicases. The helicase and exonuclease activities of the Werner protein (WRN) suggest that it functions in DNA transactions, but the physiological function of WRN remains elusive. We present several lines of evidence that WRN interacts specifically with the p50 subunit of polymerase δ, the major DNA polymerase required for chromosomal DNA replication. P50, identified by yeast two-hybrid screening, interacts physically with the C terminus of WRN. Native WRN protein coimmunoprecipitates with p50 in a cellular fraction enriched in nucleolar proteins, and this immunocomplex also includes p125, the catalytic subunit of polymerase δ. In subcellular localization studies of cells transfected with WRN, p50 and p125 redistribute to the nucleolus and colocalize with WRN. These results suggest that one of the functions of WRN protein is to directly modify DNA replication via its interaction with p50 and abet dynamic relocalization of the DNA polymerase δ complexes within the nucleus. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 97 (21), 11365-11370, 2000-10-10
Proceedings of the National Academy of Sciences