Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase

Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. Early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. However, recent studies have suggested additional roles for telomerase components in transcription and the response to DNA damage. To examine these potential telomere length maintenance-independent roles of telomerase components, we examined first generation mTR(−/−) and mTERT(−/−) mice with long telomeres. We used gene expression profiling and found no genes that were differentially expressed in mTR(−/−) G1 mice and mTERT(−/−) G1 mice compared with wild-type mice. We also compared the response to DNA damage in mTR(−/−)G1 and mTERT(−/−) G1 mouse embryonic fibroblasts, and found no increase in the response to DNA damage in the absence of either telomerase component compared to wild-type. We conclude that, under physiologic conditions, neither mTR nor mTERT acts as a transcription factor or plays a role in the DNA damage response.