Telomere

Telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos (end) and merοs (part). For vertebrates, the sequence of nucleotides in telomeres is TTAGGG, with the complementary DNA strand being AATCCC, with a single-stranded TTAGGG overhang. This sequence of TTAGGG is repeated approximately 2,500 times in humans. In humans, average telomere length declines from about 11 kilobases at birth to less than 4 kilobases in old age, with average rate of decline being greater in men than in women.

Structure and function

During chromosome replication, the enzymes that duplicate DNA cannot continue their duplication all the way to the end of a chromosome, so in each duplication the end of the chromosome is shortened (this is because the synthesis of Okazaki fragments requires RNA primers attaching ahead on the lagging strand). The telomeres are disposable buffers at the ends of chromosomes which are truncated during cell division; their presence protects the genes before them on the chromosome from being truncated instead. The telomeres themselves are protected by a complex of shelterin proteins, as well as by the RNA that telomeric DNA encodes.

Telomere shortening

In humans, average telomere length declines from about 11 kilobases at birth to less than 4 kilobases in old age, with the average rate of decline being greater in men than in women. During this process of cellular aging, functional telomeres mask the chromosome ends from the DNA damage response (DDR) and from inappropriate processing by the DNA repair machinery. These chromosome end protection functions of telomeres are essential for maintaining the stability of genomes.

Telomerase

Telomerase is the enzyme capable of elongating telomeres. Most cells do not express telomerase, so as normal human cells divide and their telomeres shorten, they lose their ability to continue dividing and become senescent or die. Some cells can become immortal through the activation of the telomerase gene, which prevents the shortening of the telomeres, and allows continued division.

See also

• DNA replication
• Senescence
• Hayflick limit
• Biological immortality

References

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