The Function of Telomere Clustering in Yeast: The Circe Effect

Recent work has shown convincingly that telomeres ofunicellular organisms, such as budding and fission yeast,Trypanosoma and Plasmodia, are spatially clustered inthe nucleus. Live imaging (Heun et al. 2001b; Tham et al.2001; Hediger et al. 2002b) and controlled in situ hybridization experiments (Gotta et al. 1996; Hediger et al.2002a) in budding yeast indicate that telomere clustersare often adjacent to the nuclear envelope (NE), althoughthey are distributed independently of nuclear pores (Fig.1A). Rather than through pores, telomeres are boundthrough two redundant mechanisms: one that requires theend-binding complex yKu, and a second that makes useof the "partitioning and anchoring domain" (PAD; Ansariand Gartenberg 1997) of the silent information regulatorSir4 (Hediger et al. 2002b; Taddei et al. 2004). This domain, which is adjacent to the lamin-like carboxyl terminus of Sir4, binds specifically to the protein Esc1 (Establishes Silent Chromatin; Andrulis et al. 2002). Esc1 islarge acidic protein localized along the inner nuclearmembrane at interpore spaces (Fig. 1B) (Taddei et al.2004). The anchorage mediated by the yKu heterodimeris not fully characterized, yet, when targeted to DNA, theyKu80 subunit is able to relocalize DNA to the nuclearperiphery in a manner independent of Sir4 or Esc1 (Taddei et al. 2004). The efficiency of yKu80-mediated anchorage varies between G1 and S phases of the cell cycle,being stronger in G1. This mechanism may reflect a linkbetween telomere anchoring and telomere end protection.In contrast to earlier reports (Galy et al. 2000; Feuerbachet al. 2002), we find that yKu does not anchor telomeresthrough interaction with the two Myosin-like proteinsMlp1 or Mlp2. Deletion of both MLP genes has no effecton telomere position, telomere silencing, or the localization of silent information regulatory proteins in buddingyeast (Fig. 2) (Hediger et al. 2002a,b). Nonetheless, Mlpproteins do have a minor effect on telomere length (Hediger et al. 2002a)...