Proposed functional domain organization of the human telomerase multimer. Schematic of hTERT-hTR, hTERT-hTERT, and hTR-hTR interactions in the human telomerase complex. RID1 is connected to the hTERT core polymerase domain (RID2, RT, and C terminus [C]) by a flexible, catalytically inessential linker. The RID2-P6.1 interaction site is likely essential for DNA synthesis. RID1-pseudoknot-template and RID1-C-terminus interactions may regulate repeat addition processivity. RID1 and the C terminus can functionally interact in trans (see text), implying that RID1 and the polymerase domain of a single hTERT may interact with different hTR molecules. P3 helix-mediated hTR dimerization also contributes to repeat addition processivity and may facilitate the allosteric regulation of one hTR monomer by the other (see text). This schematic is based on the recently proposed hTR dimer structure (40). Contacts between RID2 and the C terminus or RT sequences (2) are not depicted in this model but could form during the dynamic rearrangements likely entailed by telomerase catalysis.