Telomere maintenance is dependent on activities required for end repair of double-strand breaks

Curr Biol. 1998 May 21;8(11):657-60. doi: 10.1016/s0960-9822(98)70253-2.

Abstract

Telomeres are functionally distinct from ends generated by chromosome breakage, in that telomeres, unlike double-strand breaks, are insulated from recombination with other chromosomal termini [1]. We report that the Ku heterodimer and the Rad50/Mre11/Xrs2 complex, both of which are required for repair of double-strand breaks [2-5], have separate roles in normal telomere maintenance in yeast. Using epistasis analysis, we show that the Ku end-binding complex defined a third telomere-associated activity, required in parallel with telomerase [6] and Cdc13, a protein binding the single-strand portion of telomere DNA [7,8]. Furthermore, loss of Ku function altered the expression of telomere-located genes, indicative of a disruption of telomeric chromatin. These data suggest that the Ku complex and the Cdc13 protein function as terminus-binding factors, contributing distinct roles in chromosome end protection. In contrast, MRE11 and RAD50 were required for the telomerase-mediated pathway, rather than for telomeric end protection; we propose that this complex functions to prepare DNA ends for telomerase to replicate. These results suggest that as a part of normal telomere maintenance, telomeres are identified as double-strand breaks, with additional mechanisms required to prevent telomere recombination. Ku, Cdc13 and telomerase define three epistasis groups required in parallel for telomere maintenance.

Publication types

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

MeSH terms

  • Antigens, Nuclear*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • DNA Helicases*
  • DNA Repair*
  • DNA Replication
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases*
  • Exodeoxyribonucleases*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genes, Fungal
  • Ku Autoantigen
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Telomerase / metabolism
  • Telomere / genetics
  • Telomere / metabolism*

Substances

  • Antigens, Nuclear
  • Cyclin B
  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • high affinity DNA-binding factor, S cerevisiae
  • Telomerase
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen