The human telomere and its relationship to human disease, therapy, and tissue engineering.
The chromosomes of eukaryotes end in a specialized complex of proteins and repetitive DNA called the telomere. Telomeres form a protective cap that prevents chromosome fusions, protects chromosome ends from degradation, and assists in positioning chromosomes in the nucleus. In the absence of replenishing mechanisms, telomeric DNA is lost during each cell cycle owing to incomplete replication, oxidative damage, and nucleolytic degradation. The ribonucleoprotein complex telomerase offsets this loss of telomeric DNA, but its activity is absent in most differentiated human cells. Thus, the aging process results in ever shortening lengths of telomeric DNA. Related to this is the requirement for a mechanism of telomeric DNA maintenance in tumors, leading to telomerase expression in >85% of all cancers cells. The integral roles of telomere biology in these pathophysiological states have substantially motivated its investigation. Here, the literature on the human telomere will be reviewed with an emphasis on the relationship to human health.
Moon
Ian K
IK
University of North Carolina, School of Pharmacy, Division of Medicinal Chemistry and Natural Products Chapel Hill, North Carolina 27599-7360, USA.
Jarstfer
Michael B
MB
D000375:Aging / Q000235:genetics; D004261:DNA Replication; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D016615:Telomere; D013812:Therapeutics; D023822:Tissue Engineering