Abstract
The ends of eukaryotic chromosomes have unique nucleoprotein structures, termed telomeres, which consist of telomeric DNA and the proteins that bind specifically to these sequences. Telomeric DNA, found in all vertebrates including humans, consists of tandem repeats of the hexanucleotide sequence (TTAGGG) n . The size of telomeric DNA varies among different species, tissues, and cell types, and ranges from a few kilobases (kb) to more than 100 kb. Telomeres are essential for maintaining genomic stability by providing a protective cap for the ends of chromosomes. Other essential function of telomeres in some cells is to prevent the loss of terminal bases at each end of chromosomal DNA following the completion of linear chromosomal DNA replication. It is known that telomerase activity in hematopoietic stem cells in bone marrow is upregulated only when the growth is stimulated by cytokines, whereas resting quiescent cells are essentially telomerase negative. Thus, it was proposed that telomerase-competent stern cells may regulate telomerase activity to maintain levels sufficient to slow but not prevent telomere shortening. The simultaneous downregulation of telomerase and the disruption of telomere maintenance mechanisms by various means might be expected to produce even greater detrimental effects on cancer cell viability.
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