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Eukaryotic telomeres normally terminate with 3′ single-stranded-DNA overhang ranging from 75 to 300 bases, which is essential for telomere maintenance and capping. Multiple proteins binding single- and double-stranded telomere DNA have been identified. [25] These function in both telomere maintenance and capping.
The existence of a compensatory mechanism for telomere shortening was first found by Soviet biologist Alexey Olovnikov in 1973, [4] who also suggested the telomere hypothesis of aging and the telomere's connections to cancer and perhaps some neurodegenerative diseases.
(A) Telomere-bound proteins involved in preventing the activation of the DNA damage response checkpoint and of DSB repair mechanisms in S. cerevisiae (top) and in humans (bottom). (B) Overview of the normal function of telomere-shelterin complexes and the pathways activated by telomere shortening. [5]
Telomere-binding proteins function to generate a T-loop, which is a specialized loop structure to cap the telomeric ends. Telomerase activity is regulated by protection of telomeres 1 (POT1). [9] They serve as a protective safeguard against premature degradation as the telomere ends are no longer hidden from damage detection.
Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences (2-15 kilobases in humans) along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 ...
This inhibitive effect seems to function in a telomere length-dependent manner; [3] that is, TERRA levels inversely correlate with increased activity of telomere elongation. In general, TERRA has been shown to be most abundant in cells with long telomeres, [ 2 ] [ 3 ] while cells with short telomeres express comparatively lower levels of ...
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Telomere length is different in different tissues and cell types of the body. [10] Developing a general telomere lengthening strategy that is effective in all tissues is a complex task; Also, understanding how different types of cells, organs and systems react to telomere manipulation is very important for developing safe and effective ...