| The MUS81 endonuclease is essential for telomerase negative cell proliferation. | |
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MedLine Citation:
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PMID: 19617716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A substantial number of human tumors (approximately 10%) are telomerase negative, and cells in such tumors have been proposed to maintain telomere length by the alternative lengthening of telomeres (ALT) pathway. Although details of the molecular mechanism of ALT are largely unknown, previous studies have shown that telomere homologous recombination (HR) is implicated in the ALT pathway. MUS81 is a DNA structure-specific recombination endonuclease and functions on aberrant DNA replication and recombination. Recently, we demonstrate that MUS81 plays a key role in the maintenance of telomeres in ALT cells (Zeng, et al. Nature Cell Biology, 2009). The MUS81 endonuclease specifically localizes to ALT-associated promyelocytic leukemia nuclear bodies (APBs) and interacts with telomeres in ALT cells. Depletion of MUS81 leads to reduced telomere recombination resulting in the growth arrest of ALT cells. The endonuclease activity of MUS81, regulated by its binding partner TRF2, is found to be essential for telomere post-replicative recombination. This study provides the first direct evidence that MUS81 specifically functions on ALT recombination-based cell survival. The specific function of MUS81 on the ALT pathway provides a potential powerful diagnostic marker and a therapeutic target for ALT tumors. |
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Authors:
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Sicong Zeng; Qin Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 8 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-21 Completed Date: 2009-10-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 2157-60 Citation Subset: IM |
Affiliation:
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Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Proliferation DNA-Binding Proteins / metabolism, physiology* Endonucleases / metabolism, physiology* Humans Protein Binding Recombination, Genetic / physiology Telomerase / metabolism* Telomere / metabolism Telomeric Repeat Binding Protein 2 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/TERF2 protein, human; 0/Telomeric Repeat Binding Protein 2; EC 2.7.7.49/Telomerase; EC 3.1.-/Endonucleases; EC 3.1.-/MUS81 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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