Mammalian telomeres end in a large duplex loop.
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.
Griffith
J D
JD
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
Comeau
L
L
Rosenfield
S
S
Stansel
R M
RM
Bianchi
A
A
Moss
H
H
de Lange
T
T
D000818:Animals; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008322:Mammals; D051379:Mice; D008958:Models, Molecular; D009692:Nucleic Acid Heteroduplexes; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D009692:Nucleic Acid Heteroduplexes; D011993:Recombinant Fusion Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA