Mammalian telomeres end in a large duplex loop. |
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Authors: | J D Griffith L Comeau S Rosenfield R M Stansel A Bianchi H Moss T de Lange |
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Institution: | Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill and Curriculum in Genetics and Molecular Biology, 27599-7295, USA. jdg@med.unc.edu |
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Abstract: | Mammalian telomeres contain a duplex array of telomeric repeats bound to the telomeric repeat-binding factors TRF1 and TRF2. Inhibition of TRF2 results in immediate deprotection of chromosome ends, manifested by loss of the telomeric 3' overhang, activation of p53, and end-to-end chromosome fusions. Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro. Electron microscopy analysis of psoralen cross-linked telomeric DNA purified from human and mouse cells revealed abundant large t loops with a size distribution consistent with their telomeric origin. Binding of TRF1 and single strand binding protein suggested that t loops are formed by invasion of the 3' telomeric overhang into the duplex telomeric repeat array. T loops may provide a general mechanism for the protection and replication of telomeres. |
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