Telomere length regulation during cloning, embryogenesis and ageing
S. Schaetzlein A and K. L. Rudolph A B
+ Author Affiliations
- Author Affiliations
A Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
B Corresponding author. Email: rudolph.lenhard@mh-hannover.de
Reproduction, Fertility and Development 17(2) 85-96 https://doi.org/10.1071/RD04112
Submitted: 1 August 2004 Accepted: 1 October 2004 Published: 1 January 2005
Abstract
Telomeres are nucleoprotein complexes at the end of eukaryotic chromosomes with an essential role in chromosome capping. Owing to the end-replication problem of DNA polymerase, telomeres shorten during each cell division. When telomeres become critically short, they loose their capping function, which in turn induces a DNA damage-like response. This mechanism inhibits cell proliferation at the senescence stage and there is evidence that it limits the regenerative capacity of tissues and organs during chronic diseases and ageing. The holoenzyme telomerase synthesises telomeric DNA de novo, but, in humans, it is active only during embryogenesis, in immature germ cells and in a subset of stem/progenitor cells during postnatal life. Telomere length can be maintained or increased by telomerase, a process that appears to be regulated by a variety of telomere-binding proteins that control telomerase recruitment and activity at the telomeres. During embryogenesis, telomerase is strongly activated at the morula/blastocyst transition. At this transition, telomeres are significantly elongated in murine and bovine embryos. Early embryonic telomere elongation is telomerase dependent and leads to a rejuvenation of telomeres in cloned bovine embryos. Understanding of the molecular mechanisms underlying this early embryonic telomere elongation programme is of great interest for medical research in the fields of regeneration, cell therapies and therapeutic cloning.
Extra keywords: Pot1, telomerase, telomere binding proteins, TRF1, TRF2.
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