Telomere

Lore & Background

Muller inferred from the breakage-first hypothesis that for the continued operation of a broken ended chromosome, the function of the terminal gene was to seal the break, and he termed this gene a 'telomere' from the Greek telos (end) and meros (part). In the early 1970s, Soviet theorist Alexey Olovnikov first recognized that chromosomes could not completely replicate their ends, known as the 'end replication problem.' He suggested that DNA sequences are lost every time a cell replicates until the loss reaches a critical level, at which point cell division ends. He also predicted that a specialized DNA polymerase could extend telomeres in immortal tissues such as germ line, cancer cells, and stem cells.

Reader's Guide

Telomeres are fundamental to understanding chromosome stability, aging, and cancer. The end replication problem, exclusive to linear chromosomes, means that without telomeres, coding sequences would be progressively lost during DNA replication. The enzyme telomerase replenishes telomere caps in germ cells, some stem cells, and certain white blood cells, and can be reactivated by somatic cell nuclear transfer. The steady shortening of telomeres in somatic cells may have a role in senescence and in the prevention of cancer, as telomeres act as a time-delay fuse. The discovery of telomeres and telomerase has profound implications for understanding cellular immortality in cancer and the limits of cell division in normal tissues. The structure of telomeres, including T-loops and G-quadruplexes, also reveals how cells protect chromosome ends from being mistaken as DNA breaks, preventing chromosomal fusion.

Did You Know?

• The term 'telomere' was coined by Hermann Joseph Muller from the Greek telos (end) and meros (part).
• Alexey Olovnikov first recognized the end replication problem in the early 1970s.
• Most prokaryotes with circular chromosomes do not possess telomeres, but a small fraction of bacterial chromosomes are linear and have telomeres.