Protection of mammalian telomeres

Oncogene. 2002 Jan 21;21(4):532-40. doi: 10.1038/sj.onc.1205080.

Abstract

Telomeres allow cells to distinguish natural chromosome ends from damaged DNA. When telomere function is disrupted, a potentially lethal DNA damage response can ensue, DNA repair activities threaten the integrity of chromosome ends, and extensive genome instability can arise. It is not clear exactly how the structure of telomere ends differs from sites of DNA damage and how telomeres protect chromosome ends from DNA repair activities. What are the defining structural features of telomeres and through which mechanisms do they ensure chromosome end protection? What is the molecular basis of the telomeric cap and how does it act to sequester the chromosome end? Here I discuss data gathered in the last few years, suggesting that the protection of human chromosome ends primarily depends on the telomeric protein TRF2 and that telomere capping involves the formation of a higher order structure, the telomeric loop or t-loop.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • Apoptosis
  • Cellular Senescence
  • Chromosome Aberrations
  • DNA Helicases*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / physiology
  • Humans
  • Ku Autoantigen
  • Models, Genetic
  • Nuclear Proteins / physiology
  • Nucleic Acid Conformation
  • Protein-Serine-Threonine Kinases / physiology
  • Recombination, Genetic
  • Saccharomyces cerevisiae Proteins*
  • Telomere / chemistry
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomeric Repeat Binding Protein 2
  • Yeasts / genetics

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Telomeric Repeat Binding Protein 2
  • high affinity DNA-binding factor, S cerevisiae
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen