Mammalian telomeres end in a large duplex loop

Cell. 1999 May 14;97(4):503-14. doi: 10.1016/s0092-8674(00)80760-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cross-Linking Reagents
  • DNA / metabolism
  • DNA / ultrastructure*
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Mammals
  • Mice
  • Models, Molecular*
  • Nucleic Acid Heteroduplexes
  • Recombinant Fusion Proteins / metabolism
  • Telomere / metabolism
  • Telomere / ultrastructure*
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2

Substances

  • Cross-Linking Reagents
  • DNA-Binding Proteins
  • Nucleic Acid Heteroduplexes
  • Recombinant Fusion Proteins
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2
  • DNA