The telomere maintenance system in B Biology Diagrams Recently determined structures of the telomere maintenance protein complexes shelterin and CST shed new light on the regulation of telomere DNA replication and chromosome end-capping, and on how The role of telomere attrition and damage in inducing permanent cell cycle arrest was further demonstrated using human fibroblasts overexpressing a mutant form of TRF2 ensures proper telomere maintenance in normal cells. At the same time, each of these features is vulnerable to mutations and dysregulation, leading to familial and sporadic
Telomeres are distinctive structures that protect the ends of linear chromosomes and ensure genome stability. They are composed of long tracks of repetitive and G-rich DNA that is bound by shelterin, a dedicated six-subunit protein complex. In somatic cells, shelterin protects telomeres from the DNA damage response and regulates telomere length. Telomere repeats are replenished by telomerase
Telomere function and regulation from mouse models to human ... Biology Diagrams
However, repair at telomeres was only observed in proliferating cells, such as BJ fibroblasts and HeLa cells. Interestingly, HeLa cells, which are faster dividing cells, display a faster repair kinetics compared to slower dividing fibroblasts, suggesting that proliferation rate is an important determinant of telomeric DSB repair (Mao et al., 2016). Telomere maintenance requires the telomerase and a network of telomere-associated proteins, (TIF), telomere end-end fusion, and ultimately cell cycle arrest, senescence, and genome instability [13, 14]. In human, telomere dysfunction has been implicated in bone marrow failure syndromes, leukemia, and cancer development [9, 10, 15
This event then stimulates DDR pathways, leading to increased expression levels of the cell cycle inhibitors p16 and p21, which in turn restrain proliferation [3,4]. Despite being shortened, these telomeres still maintain an adequate number of telomere-binding proteins to prevent fusion and block DNA repair [5-8]. This process fuels a Summary of mechanisms by which the DNA damage response is repressed at telomeres or harnessed to facilitate telomerase-mediated telomere maintenance. (A) Shelterin protects telomeres from inappropriately activating a DNA damage response in phases of the cell cycle when the telomere can fold into a t-loop. TRF2 promotes t-loop formation, which The telomere-shelterin complexes that cap all eukaryotic chromosomes ensure that healthy cells can progress through the cell cycle by preventing the cellular DNA damage response from identifying chromosome ends as double-stranded breaks (DSBs). [4] [5] Without a protective cap, chromosome ends would appear identical to intrachromosomal DSBs.These DSBs activate a DNA damage response pathway
