Maintenance of chromosome ends by telomerase in Saccharomyces cerevisiae
The ends of chromosomes (telomeres) constitute a tiny fraction of DNA in a cell, but play a central role in genome stability and cellular lifespan. Following conventional DNA replication, processing of the leading strand results in chromosome shortening. A ribonucleoprotein enzyme, telomerase, replenishes these terminal sequences. Yeast telomerase contains an RNA that provides the template for addition of DNA to chromosome ends, a catalytic protein subunit (Est2p), and other essential protein components (Est1p and Est3p). Telomerase activity is tightly regulated in the cell cycle, occurring only in late S phase. We have shown that Est1p is degraded by the proteasome during G1 phase, precluding telomerase assembly. Inhibiting Est1p degradation allows Est1p to associate with the catalytic core of the telomerase complex and simultaneously recruits Est3p. Our current work is directed toward understanding the regulation of Est1p degradation, determining the mechanism through which Est1p recruits Est3p to the telomerase complex, and examining the role of Est3p in telomerase activation.