Length Does Not Matter

Abstract

The role of telomeres in maintaining genetic stability was first described by Blackburn1 in 1991. Telomeres and their associated proteins provide protection against DNA degradation because 40 to 200 bp of the telomere's tandem repeats are lost on each successive cell division, resulting in the progressive shortening of chromosomes. Telomeres also help to regulate the “cellular clock” because critically short telomeres trigger a cell cycle checkpoint, resulting in replicative senescence (ie, a natural process for terminally differentiated somatic cells, yet undesirable for hematopoietic cells, which require the potential for regulated proliferation throughout life).2 Thus, exquisite regulation of telomerase is required for extension of telomeres under appropriate conditions in immune cells. Indeed, overexpression or underexpression of telomerase or its reverse transcriptase catalytic domain, human telomerase reverse transcriptase (hTERT), is associated with numerous chronic inflammatory and autoimmune disorders,3 underscoring the importance of telomerase activity in immune cell function. See accompanying article on page 245 Nearly 10 years ago, Stewart et al4 demonstrated a novel role for telomerase in the promotion of tumorigenesis. By using an hTERT-mutant protein unable to extend telomere length, the researchers showed that TERT, together with transforming protein p21 (H-RAS), induced tumorigenesis independently of effects on telomeres. Adding further complexity to telomerase activity, recent work from Park et al5 showed that TERT associates with Brahma-related gene …