Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells

Nucleic Acids Res. 2004 Jul 16;32(12):3743-51. doi: 10.1093/nar/gkh691. Print 2004.


For cells on the path to carcinogenesis, the key to unlimited growth potential lies in overcoming the steady loss of telomeric sequence commonly referred to as the 'end-replication problem' that occurs with each cell division. Most human tumors have reactivated telomerase, a specialized reverse transcriptase that directs RNA-templated addition of telomeric repeats on to chromosomal termini. However, approximately 10% of tumors maintain their telomeres through a recombination-based mechanism, termed alternative lengthening of telomeres or ALT. Here we demonstrate that telomeric DNA undergoes a high rate of a particular type of recombination visualized cytogenetically as sister chromatid exchange (SCE), and that this rate is dependent on genotype. A novel model of ALT is presented in which it is argued that telomeric exchanges, if they are unequal and occur at a sufficiently high frequency, will allow cells to proliferate indefinitely without polymerase-mediated extension of telomeric sequence.

Publication types

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

MeSH terms

  • Animals
  • Cell Division
  • Cells, Cultured
  • Cellular Senescence
  • DNA / genetics
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Recombination, Genetic*
  • Sister Chromatid Exchange
  • Telomerase / analysis
  • Telomere / genetics*


  • DNA
  • Telomerase