Cell cycle-dependent regulation of yeast telomerase by Ku

Nat Struct Mol Biol. 2004 Dec;11(12):1198-205. doi: 10.1038/nsmb854. Epub 2004 Nov 7.

Abstract

The heterodimeric Ku complex affects telomere structure in diverse organisms. We report here that in the absence of Ku, the catalytic subunit of telomerase, Est2p, was not telomere-associated in G1 phase, and its association in late S phase was decreased. The telomere association of Est1p, a telomerase component that binds telomeres only in late S phase, was also reduced in the absence of Ku. The effects of Ku on telomerase binding require a 48-nucleotide (nt) stem-loop region of TLC1 telomerase RNA. Ku interacts with TLC1 RNA via this 48-nt region throughout the cell cycle, but this interaction was reduced after telomere replication. These data support a model in which Ku recruits telomerase to telomeres in G1 phase when telomerase is inactive and promotes telomerase-mediated telomere lengthening in late S phase.

Publication types

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

MeSH terms

  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism*
  • Cell Cycle*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Ku Autoantigen
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism
  • RNA, Fungal / chemistry
  • RNA, Fungal / metabolism
  • S Phase
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telomerase / chemistry
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / metabolism
  • Telomere-Binding Proteins / metabolism

Substances

  • Antigens, Nuclear
  • Cdc13 protein, S cerevisiae
  • DNA-Binding Proteins
  • RNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • telomerase RNA
  • RNA
  • Telomerase
  • Ku Autoantigen