Long G Tails at Both Ends of Human Chromosomes Suggest a C Strand Degradation Mechanism for Telomere Shortening

Cell. 1997 Mar 7;88(5):657-66. doi: 10.1016/s0092-8674(00)81908-x.

Abstract

The chromosomes of lower eukaryotes have short telomeric 3' extensions. Using a primer-extension/nick-translation technique and nondenaturing hybridization, we find long 3' G-rich tails at human chromosome ends in mortal primary fibroblasts, umbilical vein endothelial cells, and leukocytes, as well as in immortalized fibroblasts. For all cells tested, >80% of the telomeres have long G-rich overhangs, averaging 130-210 bases in length, in disagreement with the conventional model for incomplete lagging-strand replication, which predicts overhangs on 50% of the chromosome ends. The observed G tails must exist during most of the cell cycle and probably result from degradation of both chromosome ends. The average lengths of the G tails are quantitatively consistent with the observed rates of human chromosome shortening.

Publication types

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

MeSH terms

  • Alkalies
  • Cell Line, Transformed
  • Cells, Cultured / physiology
  • Chromosomes / physiology*
  • DNA Primers
  • DNA-Directed DNA Polymerase
  • Electrophoresis, Agar Gel
  • Electrophoresis, Gel, Two-Dimensional
  • Fetus / cytology
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Guanine / analysis
  • Humans
  • Lung / cytology
  • Nucleic Acid Hybridization
  • RNA-Directed DNA Polymerase
  • Taq Polymerase
  • Telomere / genetics*
  • Telomere / metabolism*

Substances

  • Alkalies
  • DNA Primers
  • Guanine
  • Taq Polymerase
  • RNA-Directed DNA Polymerase
  • DNA-Directed DNA Polymerase