telomerase
Definition: Telomerase is a multimeric ribonucleoprotein complex consisting of at least a functional RNA (hTR) that contains the template region complementary to the telomeric sequence and a reverse transcriptase protein component (hTERT) that catalyzes the addition of telomeric repeats to the ends of chromosomes.
hTR is expressed in all tissues but hTERT is only highly expressed in specific germ line cells, proliferative stem cells of renewal tissues, and immortal cancer cells.
Functions
Telomeres are repetitive, non-coding DNA [TTAGGG] elements at the ends of chromosomes. In most human somatic cells, telomeres shorten with each cell division due to incomplete lagging DNA strand synthesis and oxidative damage.
Even cells that express telomerase (e.g. peripheral blood mononuclear cells and other stem-like cells) undergo telomere shortening with age.
Telomere lengths are affected by their starting set points, the cellular activity of telomerase, the cell’s history of cell division and environmental effects. Overexpression of the catalytic subunit of human telomerase (hTERT) induces telomerase activity and telomere elongation.
Chromosome stability requires a dynamic balance of DNA loss and gain in each terminal tract of telomeric repeats. Repeat addition by a specialized reverse transcriptase, telomerase, has an important role in maintaining this equilibrium.
Pathology of telomerases (Telomerase disease)
cancer
X-linked, autosomal dominant forms of congenital dyskeratosis
- The X-linked form is due to mutations in the DKC1 gene at Xq28. The encoded protein, dyskerin, is a component of both small nucleolar ribonuclear protein particles and the telomerase complex. Mutations in DKC1 mainly lead to amino acid substitutions.
- The autosomal dominant form of the disease is due to mutations in hTR, the RNA component of telomerase, making it likely that the disease is due to defective telomerase activity. Mutations in hTR are predicted to either disrupt secondary structure or alter the template region.
recessive forms : no genes known (2003)
References
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