Is there a telomere-bound 'EST' telomerase holoenzyme?

Eukaryotic linear chromosomes culminate in nucleoprotein structures designated telomeres. The terminal telomeric DNA consists of tandem repeats of a G-rich motif that is established and maintained by the action of the specialized reverse transcriptase telomerase. In addition to the core enzyme, effective replication of telomeric DNA requires a number of regulatory factors. In budding yeast, four components identified in the seminal Ever Shorter Telomere (EST) genetic screens constitute the keystone proteins that sustain telomeric DNA. Importantly, the EST proteins appear to be structurally conserved from yeast to human. The mechanism of telomerase recruitment and regulation, with an emphasis on the EST proteins, are discussed in this review.