The Fanconi Anemia Pathway Promotes Replication-Dependent DNA Interstrand Cross-Link Repair
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- Puck Knipscheer
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
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- Markus Räschle
- Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
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- Agata Smogorzewska
- Department of Genetics, Harvard Medical School, and Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA.
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- Milica Enoiu
- Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
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- The Vinh Ho
- Departments of Pharmacological Sciences and Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
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- Orlando D. Schärer
- Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
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- Stephen J. Elledge
- Department of Genetics, Harvard Medical School, and Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA.
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- Johannes C. Walter
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
説明
<jats:title>Fanconi Cross-Links</jats:title> <jats:p> Fanconi anemia is a rare genetic disease characterized by bone marrow failure, developmental abnormalities, and dramatically increased cancer susceptibility. Cells derived from Fanconi anemia patients are sensitive to agents that cause DNA interstrand cross-links, indicating that under normal circumstances the Fanconi pathway controls the repair of these DNA lesions. <jats:bold> Knipscheer <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1698" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1182372">1698</jats:related-article> , published online 12 November) found that two Fanconi anemia proteins, FANCI and FANCD2, promoted the DNA replication–coupled repair of interstrand cross-links in cell extracts. The FANCI-FANCD2 complex was required for the incisions that unhook the cross-link and for the insertion of a nucleotide across from the damaged template base during lesion bypass. </jats:p>
収録刊行物
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- Science
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Science 326 (5960), 1698-1701, 2009-12-18
American Association for the Advancement of Science (AAAS)