Saturday, December 10, 2016

Immortal: Mechanisms of Telomere Repair in Cancer Cells

Cancer cells are immortal. This means that given the proper environment, cancerous cells will divide indefinitely. They do this by continuously repairing telomeres, which would otherwise gradually shorten over repeated replications and eventually prevent the cell from replicating its DNA. The majority of cancer cells use the enzyme telomerase, which repairs shortened telomeres by working in concert with polymerase to add telomeric repeats to the ends of the chromosome. However, a significant portion of cancerous tumors (ab. 10-15%) use an alternative method known as alternative lengthening of telomeres or ALT. 

ALT is based on another form of DNA repair -homologous recombination- used by organisms that lack telomerase. There are two models proposed for the ALT process:
     1. Unequal sharing of telomeric DNA during homologous recombination results in homologs with short telomeres, and homologues with long telomeres. The cells with longer telomeres eventually out compete the cells with shortened telomeres.
     2. DNA is synthesized from template telomeric DNA; either from another telomere or extrachromosomal DNA molecules.
To better understand the mechanisms underlying ALT, Robert Dilley et al induced breaks in ALT cell telomeres using a nuclease attached to a telomere binding protein. Telomere synthesis increased tenfold, and the manner of synthesis mimicked that of the second proposed model.

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