Oxidative DNA Damage and Telomere Shortening
Telomeres are highly complex DNA-protein structures that protect the ends of chromosomes. A variety of DNA damage response and repair proteins are bound to telomeres and fulfil functions in the maintenance of the telomeric cap, in the protection of chromosomes from end-to-end fusion and, if telomeres become uncapped, in the induction and translation of a senescence signal. Telomeres shorten with cell division. This shortening is to a large extent caused by the accumulation of telomeric single-strand breaks. The telomeric DNA structure, with its high density of guanine repeats, results in an enhanced vulnerability towards DNA damage, especially oxidative damage. Moreover, repair of single-strand breaks in tolomeres is less efficient than in the bulk of the genome, and this is dependent on TRF2 expression. Thus, telomeres act as cellular sentinels: by shortening and arresting cell proliferation in response to accumulated oxidative stress they protect cells and tissues from the adverse consequences of genomic damage.
KeywordsTelomere Length Single Strand Break Human Diploid Fibroblast Holliday Junction Telomere Loss
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