Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Nat Struct Mol Biol. 2015 Nov;22(11):875-80. doi: 10.1038/nsmb.3106. Epub 2015 Nov 4.


Alternative lengthening of telomeres (ALT) involves homology-directed telomere synthesis. This multistep process is facilitated by loss of the ATRX or DAXX chromatin-remodeling factors and by abnormalities of the telomere nucleoprotein architecture, including altered DNA sequence and decreased TRF2 saturation. Induction of telomere-specific DNA damage triggers homology-directed searches, and NuRD-ZNF827 protein-protein interactions provide a platform for the telomeric recruitment of homologous recombination (HR) proteins. Telomere lengthening proceeds by strand exchange and template-driven DNA synthesis, which culminates in dissolution of HR intermediates.

Publication types

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

MeSH terms

  • DNA Helicases / metabolism
  • Homologous Recombination
  • Nuclear Proteins / metabolism
  • Telomere / metabolism*
  • Telomere Homeostasis*


  • Nuclear Proteins
  • DNA Helicases