Telomeres and chromosome stability

Abstract

The discovery of telomeres, originating from the Greek words “telos” (end) and “meros” (part), was the unexpected outcome of a simple experiment conducted by Hermann J. Müller in the 1930s (Müller 1938). This brilliant geneticist irradiated Drosophila chromosomes and made the astonishing observation that the ends of the DNA, unlike the rest of the genome, evade aberrant genomic modifications such as inversions and deletions, suggesting the presence of a protective mechanism. In 1941, the famous geneticist Barbara McClintock’s work further strengthened the importance of telomeres in the maintenance of genome integrity (McClintock 1941). Using a special Zea mays strain characterized by high frequencies of chromosomal breakage and fusion, she readily saw the appearance of dicentric chromosomes. Surprisingly, she also noted that chromosome ends are protected from fatal “rupture-fusion-bridge” cycles by the addition of new DNA. In the 1980s, the combination of Blackburn, Greider and Szostak’s experiments revealed that the telomere is composed of short tandem G-rich hexameric repeats that are evolutionarily and functionally conserved across different organisms (Szostak and Blackburn 1982). Their work also led to the discovery of telomerase, the enzyme responsible for telomere synthesis (Greider and Blackburn 1985).