How long does telomerase extend telomeres? Regulation of telomerase release and telomere length homeostasis

Abstract

Telomerase, the enzyme that replenishes telomeres, is essential for most eukaryotes to maintain their generations. Telomere length homeostasis is achieved via a balance between telomere lengthening by telomerase, and erosion over successive cell divisions. Impaired telomerase regulation leads to shortened telomeres and can cause defects in tissue maintenance. Telomeric DNA is composed of a repetitive sequence, which recruits the protective protein complex, shelterin. Shelterin, together with chromatin remodelling proteins, shapes the heterochromatic structure at the telomere and protects chromosome ends. Shelterin also provides a foothold for telomerase to be recruited and facilitates telomere extension. Such mechanisms of telomere recruitment and activation are conserved from unicellular eukaryotes to humans, with the rate of telomere extension playing an important role in determining the length maintained. Telomerase can be processive, adding multiple telomeric repeats before dissociating. However, a question remains: how does telomerase determine the number of repeats to add? In this review, I will discuss about how telomerase can monitor telomere extension using fission yeast as a model. I propose a model whereby the accumulation of the Pot1 complex on the synthesised telomere single-strand counteracts retention of telomerase via chromatin proteins and the similar system may be conserved in mammals.

Telomeres and Telomere Length: A General Overview

“…On average, a single human telomere contains enough repeats to buttress the effect of telomere erosion in the absence of a maintenance mechanism, with an estimated loss of about 50 to 250 bp per mitosis [12,90,94]. Telomere shortening, to an extent, in proliferating cells of self-renewal tissues, such as hematopoietic cells, cells of the skin, and cells from gastrointestinal epithelium, is mitigated by holoenzyme telomerase [5,12,95]. Most of the adult stem cells and somatic tissues do not contain sufficient telomerase to maintain telomere length infinitely and therefore undergo age-related telomere shortening [96].…”

Developing Novel G-Quadruplex Ligands: From Interaction with Nucleic Acids to Interfering with Nucleic Acid–Protein Interaction

“…Eukaryotic chromosomes become shorter and shorter during replication with cell division, which eventually leads to cell senescence and apoptosis [72]. In most eukaryotes, the telomeres recruit telomerase to compensate for cellular damage [73]. Specifically, telomere DNA exists as a single-stranded overhang and serves as the substrate for reverse transcription catalyzed by the telomerase.…”

Telomerase and Telomeres Biology in Thyroid Cancer

“…Furthermore, Shelterins protect telomeres from end-to-end fusion events and degradation [3]. Finally, TPP1 functions by regulating telomerase access to telomere, and the entire complex regulates nucleosomes distribution and contributes to the establishment of an epigenetic environment prone to telomere maintenance [4,5].…”