Telomerase Inhibition for Killing Cancer Cells

There is an upper limit to the number of times a cell can divide before it stops growing and enters a phase which is called senescence. For human embryonic diploid fibroblasts, the Hayflick limit is about 60 doublings. This limit is related to the end-replication problem faced by DNA polymerase as it moves along a template strand synthesizing a new strand. DNA polymerase must initiate synthesis from an RNA primer and it synthesizes a new strand beginning with the primers 3 end. The need for the RNA primer means that the DNA polymerase cannot replicate the very 5 end of the lagging strand because the primer occupies the last few bases of the template strand. As a consequence, the DNA of a chromosome shortens by 50-100 nucleotides each time the chromosome replicates. Eukaryotic chromosomes have telomeres at their ends, which are long sections made up of a repeat sequences, TTAGGG in human cells. These sequences protect the ends of the chromosomes, thus preventing the chromosomes from interacting with each other. Telomeres are eroded with each division until they no longer function properly, with catastrophic results for the cell.