Mammalian telomeres end in a large duplex loop

Mammalian telomeres contain a duplex array of telomeric repeats bound to th e telomeric repeat-binding factors TRF1 and TRF2. Inhibition of TRF2 result s in immediate deprotection of chromosome ends, manifested by loss of the t elomeric 3' overhang, activation of p53, and end-to-end chromosome fusions. Electron microscopy reported here demonstrated that TRF2 can remodel linea r telomeric DNA into large duplex loops (t loops) in vitro. Electron micros copy analysis of psoralen cross-linked telomeric DNA purified from human an d mouse cells revealed abundant large t loops with a size distribution cons istent with their telomeric origin. Binding of TRF1 and single strand bindi ng protein suggested that t loops are formed by invasion of the 3' telomeri c overhang into the duplex telomeric repeat array. T loops may provide a ge neral mechanism for the protection and replication of telomeres.