telomerase

Function

• RNA-dependent DNA polymerase
• adds repeated arrays of the sequence TTAGGG to 5'ends of linear DNA to form telomeres.
• maintains telomere ends during replicative DNA synthesis
• telomerase contains an RNA template as an integral component of the enzyme complex
• DNA replication proceeding in the 5'-> 3' direction requires an RNA primer for intitiation, therefore it leaves a stretch of unreplicated DNA at the 5'end of linear DNA
• this leads to a loss of terminal telomeric repeats with every S-phase, with shortening of telomeres ~100 base pairs per cell division.
• in germ cell lines & in some tissues, telomere length is maintained by telomerase activity
• in many cells & tissues, telomerase activity is low or absent resulting in telomere loss with each cell division
• this limits the replicative capacity of cells, but also prevents outgrowth of a transformed cell into an immortal malignant cell.

Structure

• subunits include TERT, DKC1, WRAP53/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 & a telomerase RNA template component (TERC)

* 3D structure

Pathology

• activation of telomerase has been implicated in cell immortalization & cancer cell pathogenesis
• inhibition has been suggested to play a role in aging, however, more likely plays a role in terminal differentiation

More general terms

• RNA-dependent DNA polymerase
• multisubunit protein

Additional terms

• telomere
• telomeres & telomerase in tumor cells