5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events

DNA Repair (Amst). 2013 Mar 1;12(3):238-45. doi: 10.1016/j.dnarep.2012.12.008. Epub 2013 Jan 21.


A subset of human tumors ensures indefinite telomere length maintenance by activating a telomerase-independent mechanism known as Alternative Lengthening of Telomeres (ALT). Most tumor cells of ALT origin share a constellation of unique characteristics, which include large stores of extra-chromosomal telomeric material, chronic telomere dysfunction and a peculiar enrichment in chromosome ends with 5' C-rich overhangs. Here we demonstrate that acute telomere de-protection and the subsequent DNA damage signal are not sufficient to facilitate formation of 5' C-overhangs at the chromosome end. Rather chromosome ends bearing 5' C-overhangs are a by-product of rapid cleavage events, processing of which occurs independently of the DNA damage response and is partly mediated through the XRCC3 endonuclease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition
  • Cell Line, Tumor
  • DNA Damage
  • DNA Repair
  • DNA, Intergenic
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / metabolism
  • Genome, Human
  • Humans
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Homeostasis*
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism
  • Werner Syndrome / metabolism


  • DNA, Intergenic
  • DNA-Binding Proteins
  • TERF2 protein, human
  • Telomeric Repeat Binding Protein 2
  • X-ray repair cross complementing protein 3