Telomere

Telomeres are specialized regions at the ends of linear chromosomes that protect genetic material during cell division. In humans, they consist of short tandem DNA repeats (TTAGGG) bound by a multi-protein complex called shelterin. This structure prevents chromosome ends from being mistaken for broken DNA and helps regulate access to the chromosome terminus.

During DNA replication, the end replication problem prevents complete duplication of the 3' end, leading to progressive shortening of telomeres with each cell division. Telomere length thus acts as a molecular clock for proliferative history in most somatic cells. When telomeres become critically short, cells typically enter replicative senescence or undergo apoptosis, contributing to tissue aging and reduced regenerative capacity.

Telomerase, a ribonucleoprotein enzyme, can counteract telomere shortening by adding telomeric repeats to chromosome ends. It comprises the catalytic protein TERT and an RNA component TERC that serves as a template. Telomerase activity is high in germ cells and many stem cells and is reactivated in a majority of cancers, but it is generally low or absent in most mature somatic cells.

Telomere dynamics are influenced by genetic and environmental factors and can serve as biomarkers of aging and disease risk. Short telomeres are associated with age-related diseases and telomere biology disorders such as dyskeratosis congenita. Alternative lengthening of telomeres (ALT) is a telomerase-independent maintenance mechanism observed in some cancers. Measurement methods include quantitative PCR, Southern blot-based assays, and fluorescence in situ hybridization.