... this study explains in a clear manner, what a certain group (and couple pooh-pooh-ers here) didn't get it right for quite some time ... it happens when you want to solve things "in your way" and you are stuck in an initial idea that proves to be not so great ... as usual, sciences moves on ...
http://www.colorado....-cancer-process
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The findings, which were recently published in the journal Cell, show that telomerase has a small window of opportunity, lasting only minutes, to do its job at the ends of chromosomes. The team was surprised to find that telomerase may probe each telomere thousands of times, rarely forming a stable connection, in order to be successful at connecting to the chromosome end. Researchers believe that inhibiting telomerase from attaching to telomeres in cancer cells is a strategy for treatment of the disease.
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“At the end of the day, the goal is to target telomerase as an approach to treat cancer,” said Schmidt. “You can inhibit telomerase across the board, but the challenge is isolating the telomerase in cancer cells from the telomerase participating in the normal processes of healthy cells. This research brings us closer to understanding these processes.”
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http://www.cell.com/...8674(16)30983-7
Highlights
- •Live cell, single-molecule imaging of doubly genome-edited cell lines
- •Telomerase uses three-dimensional diffusion to search for telomeres
- •Telomerase forms short, dynamic and long, static interactions with telomeres
- •Observations provide a new model for human telomerase recruitment to telomeres
Telomerase maintains genome integrity by adding repetitive DNA sequences to the chromosome ends in actively dividing cells, including 90% of all cancer cells. Recruitment of human telomerase to telomeres occurs during S-phase of the cell cycle, but the molecular mechanism of the process is only partially understood. Here, we use CRISPR genome editing and single-molecule imaging to track telomerase trafficking in nuclei of living human cells. We demonstrate that telomerase uses three-dimensional diffusion to search for telomeres, probing each telomere thousands of times each S-phase but only rarely forming a stable association. Both the transient and stable association events depend on the direct interaction of the telomerase protein TERT with the telomeric protein TPP1. Our results reveal that telomerase recruitment to telomeres is driven by dynamic interactions between the rapidly diffusing telomerase and the chromosome end.
