Expression of the catalytic subunit of @entity1 telomerase, @entity2215 , extends @entity1 primary fibroblast life span. Such life span extension has generally been reported to be accompanied by net telomere lengthening, which led to the hypothesis that it is the telomere lengthening that causes the life span extension. Here we show that @entity2215 +C and @entity2215 -FlagC, mutant telomerase proteins with either 10 additional residues or a FLAG epitope added to the @entity2215 C-terminus, confer significant but limited life span extension to IMR90 @entity1 primary lung fibroblasts. However, as the cells continue to grow for >100 population doublings past their normal senescence point, bulk telomere length continues to erode to lengths much shorter than those seen at the senescence of control telomerase-negative cells. Expression of @entity2215 +C immortalized IMR90 cells transformed by three different oncogenes. Again, bulk telomeres became much shorter than those of the control cells at crisis. Additional @entity2215 mutants were constructed and analyzed similarly. Enzymatically active @entity2215 - @entity70001 + @entity70002 , like other previously reported conserved GQ domain mutants and C-terminally HA-tagged @entity2215 , failed to extend life span. Another GQ domain mutant, @entity2215 - @entity70003 , was indistinguishable from wild-type @entity2215 in its cell growth effects, but there was no net telomere lengthening. These results uncover further @entity2215 allele-specific phenotypes that uncouple telomerase activity, net telomere lengthening and life span extension.

Catalytically active XXXX telomerase mutants with allele-specific biological properties.

@entity1 :: ('9606', 'Species') :: ['human'] @entity70001 :: ('p|SUB|N|125|A', 'ProteinMutation') :: ['N125A'] @entity70003 :: ('p|SUB|E|79|A', 'ProteinMutation') :: ['E79A'] @entity70002 :: ('c|SUB|T|126|A', 'DNAMutation') :: ['T126A'] @entity2215 :: ('7015', 'Gene') :: ['hTERT']
@entity1 :: (9606,Species) :: ['human']
