Telomere dynamics in human cells

Biochimie. 2008 Jan;90(1):116-21. doi: 10.1016/j.biochi.2007.08.003. Epub 2007 Aug 11.

Abstract

Human telomeres are intrinsically dynamic structures, with multiple biological processes operating to generate substantial length heterogeneity. Processes that operate specifically at the terminus, that include the end-replication problem coupled with C-strand resection, result in gradual telomere erosion with ongoing cell division. Rates of telomere erosion can be modulated by cell culture conditions and pleiotropic effects. Other processes, that are not consistent with the end replication problem, generate sporadic large-scale changes in telomere length. These events are detected in normal human cells and tissues; the severely truncated telomeres that result are potentially fusogenic and may lead to the types of genetic rearrangements that typify early-stage neoplasia. The processes that underlie sporadic telomeric deletion are unclear, but may include intra-allelic recombination within the T-loop structure, unequal sister chromatid exchange and replication fork stalling. The relative contributions of these processes in the generation of the heterogeneous telomere length profiles observed in human cells are discussed.

Publication types

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

MeSH terms

  • Alleles
  • Cell Proliferation
  • Cells, Cultured
  • Chromosomes, Human / ultrastructure
  • DNA Replication
  • Humans
  • Recombination, Genetic
  • Telomere / genetics
  • Telomere / physiology*
  • Telomere / ultrastructure
  • Telomere-Binding Proteins / metabolism

Substances

  • Telomere-Binding Proteins