Abstract
Telomeres are a unique structure of DNA repeats covered by proteins at the ends of the chromosomes that protect the coding regions of the genome and function as a biological clock. They require a tight regulation of the factors covering and protecting their structure, as they are shortened with each cell division to limit the ability of cells to replicate uncontrollably. Additionally, they protect the chromosome ends from DNA damage responses and thereby, prevent genomic instability. Telomere dysfunction can lead to chromosomal abnormalities and cancer. Therefore, dysregulation of any of the factors that regulate the integrity of the telomeres will have implications to chromosomal stability, replicative lifespan and may lead to cell transformation. This review will cover the main factors participating in the normal function of the telomeres and how these are regulated by the ubiquitin and SUMO systems. Accumulating evidence indicate that the ubiquitin and SUMO pathways are significant regulators of the shelterin complex and other chromatin modifiers, which are important for telomere structure integrity. Furthermore, the crosstalk between these two pathways has been reported in telomeric DNA repair. A better understanding of the factors contributing to telomere biology, and how they are regulated, is important for the design of new strategies for cancer therapies and regenerative medicine.
Highlights
Telomeres are DNA structures covered by proteins at the ends of the chromosomes that serve several key biological functions
They function as a ‘biological clock’ that regulates the replicative lifespan of cells, as well as protect the integrity of the ends of the chromosomes from nucleolytic digestion (Vaziri et al, 1994; Vaziri and Benchimol, 1996; Karlseder et al, 1999; O’Sullivan and Karlseder, 2010)
The function of the telomeres as a biological clock requires a tight regulation of the factors covering and protecting their structure, in order to limit the ability of cells to replicate uncontrollably
Summary
Telomeres are DNA structures covered by proteins at the ends of the chromosomes that serve several key biological functions. They function as a ‘biological clock’ that regulates the replicative lifespan of cells, as well as protect the integrity of the ends of the chromosomes from nucleolytic digestion (Vaziri et al, 1994; Vaziri and Benchimol, 1996; Karlseder et al, 1999; O’Sullivan and Karlseder, 2010). Dysfunctions or disruptions of those nucleoprotein structures at the end of the chromosomes can present as serious pathologies These telomere syndromes span several different disease areas including blood, lung and liver disease, bone marrow failure, age related disease, and cancer. Understanding the mechanisms that regulate telomere length will help guide diagnosis, prevention and treatment
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