Taz1 enforces cell-cycle regulation of telomere synthesis.
The dramatic telomerase-dependent overelongation of telomeres in cells lacking Taz1 (ortholog of human TRF1/TRF2) or Rap1 implicates these proteins in restraint of telomerase activity. However, the modes by which these proteins regulate telomerase remain mysterious. Here we show that the mechanisms underlying excessive telomerase activity differ markedly between taz1Δ and rap1Δ strains. Despite allowing elevated telomerase access, rap1Δ telomeres are processed and synthesized in a cell-cycle-constrained manner similar to that of wild-type cells. In contrast, taz1Δ telomeres are processed with little cell-cycle dependency and recruit telomerase over an abnormally wide range of cell-cycle stages. Furthermore, although taz1Δ telomeres experience transient attrition mediated by replication fork stalling, this is balanced not only by temporal expansion of the telomerase activity period, but also by markedly increased recruitment of telomerase and its accessory factor Est1, suggesting that stalled forks generate robust substrates for telomerase.
Telomere Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, WC2A 3LY, London, UK.
Pierre-Marie
PM
Dehé
Ofer
O
Rog
Miguel Godinho
MG
Ferreira
Jessica
J
Greenwood
Julia Promisel
JP
Cooper
D004261:DNA Replication; D006801:Humans; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe; D019098:Telomerase