Positive and negative regulation of telomerase access to the telomere

The protective caps on chromosome ends - known as telomeres - consist of DN A and associated proteins that are essential for chromosome integrity. A fu ndamental part of ensuring proper telomere function is maintaining adequate length of the telomeric DNA tract, Telomeric repeat sequences are synthesi zed by the telomerase reverse transcriptase, and, as such, telomerase is a central player in the maintenance of steady-state telomere length. Evidence from both yeast and mammals suggests that telomere-associated proteins pos itively or negatively control access of telomerase to the chromosome termin us. In yeast, positive regulation of telomerase access appears to be achiev ed through recruitment of the enzyme by the end-binding protein Cdc13p, In contrast, duplex-DNA-binding proteins assembled along the telomeric tract e xert a feedback system that negatively modulates telomere length by limitin g the action of telomerase. In mammalian cells, and perhaps also in yeast, binding of these proteins probably promotes a higher-order structure that r enders the telomere inaccessible to the telomerase enzyme.