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Resolving the question of why cancer cells have short telomeres led to the development of a two-stage model for how cancer cells subvert telomeric regulation of the cell cycle. First, the DNA damage checkpoint must be inactivated to allow cells to continue dividing even when telomeres pass the critical length threshold.
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 role of telomeres and telomerase in cell aging and cancer was established by scientists at biotechnology company Geron with the cloning of the RNA and catalytic components of human telomerase [9] and the development of a polymerase chain reaction (PCR) based assay for telomerase activity called the TRAP assay, which surveys telomerase ...
Alternative Lengthening of Telomeres (also known as "ALT") is a telomerase-independent mechanism by which cancer cells avoid the degradation of telomeres.. At each end of the chromosomes of most eukaryotic cells, there is a telomere: a region of repetitive nucleotide sequences which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.
Telomeres at the end of a chromosome. The relationship between telomeres and longevity and changing the length of telomeres is one of the new fields of research on increasing human lifespan and even human immortality. [1] [2] Telomeres are sequences at the ends of chromosomes that shorten with each cell division and determine the lifespan of ...
Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. In addition to cancer cells, tumors exhibit another dimension of complexity: they incorporate a community of recruited, ostensibly normal cells that contribute to ...
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat.
The MRN complex's biological role in telomere maintenance has prompted research linking MRN to cancer cell immortality. In human HNSCC cell lines, disruption of the Nbs1 gene (which downregulates expression of the entire MRN complex), has resulted in reduced telomere length and persistent lethal DNA damage in these cells. [33]