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Abstract
Bacteria and viruses possess circular DNA, whereas eukaryotes with typically very large DNA molecules have had to evolve into linear chromosomes to circumvent the problem of supercoiling circular DNA of that size. Consequently, such organisms possess telomeres to cap chromosome ends. Telomeres are essentially tandem repeats of any DNA sequence that are present at the ends of chromosomes. Their biology has been an enigmatic one, involving various molecules interacting dynamically in an evolutionarily well-trimmed fashion. Telomeres range from canonical hexameric repeats in most eukaryotes to unimaginably random retrotransposons, which attach to chromosome ends and reverse-transcribe to DNA in some plants and insects. Telomeres invariably associate with specialised protein complexes that envelop it, also regulating access of the ends to legitimate enzymes involved in telomere metabolism. They also transcribe into repetitive RNA which also seems to be playing significant roles in telomere maintenance. Telomeres thus form the intersection of DNA, protein, and RNA molecules acting in concert to maintain chromosome integrity. Telomere biology is emerging to appear ever more complex than previously envisaged, with the continual discovery of more molecules and interplays at the telomeres. This review also includes a section dedicated to the history of telomere biology, and intends to target the scientific audience new to the field by rendering an understanding of the phenomenon of chromosome end protection at large, with more emphasis on the biology of human telomeres. The review provides an update on the field and mentions the questions that need to be addressed.
Highlights
Telomeres–Historical PerspectiveIn 1938, at a time when even the composition of genetic material was unknown, the existence of a special structure at the ends of chromosomes was first speculated in a lecture given by Hermann
Bacteria and viruses possess circular DNA, whereas eukaryotes with typically very large DNA molecules have had to evolve into linear chromosomes to circumvent the problem of supercoiling circular DNA of that size
Loss of shelterin proteins can lead to DNA damage response (DDR), TRF2, and POT1 directly serving to inhibit ATM and ATR kinases, respectively, and a loss of TRF2 or POT1 would de-repress the association of ATM/ATR to the telomeres, resulting in senescence or apoptosis
Summary
In 1938, at a time when even the composition of genetic material was unknown, the existence of a special structure at the ends of chromosomes was first speculated in a lecture given by Hermann. The same observation in yeast by Szostak and Blackburn, upon introduction of telomere-containing linear DNA from Tetrahymena, a completely unrelated species, highlighted the maintenance of chromosomal integrity by telomeres as a fundamental cellular mechanism [8]. This would soon lead to the unravelling of a distinct pattern conserved across all eukaryotes—a guanosine-rich hexameric. We discuss below all of the fundamental aspects of telomeres, beginning with the bare bones—the telomere sequence
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