Telomerase Interactions with DNA

One of the unique properties of telomerase is its ability to add multiple “blocks” of telomeric DNA to the telomere in a repetitive manner.  It does this using a “racheting” motion, with several parts of the enzyme maintaining contact with the DNA throughout the process.

The number and location of these DNA “anchor sites” has been the subject of much investigation, since it is possible that they may represent one avenue to block telomerase from accessing the telomere.  However, this research in the telomerase field has been hampered by technical difficulties in producing large amounts of the enzyme in a test-tube.

We have successfully developed a way to quantitatively measure the interaction of telomerase and DNA using very small amounts of enzyme.  This has enabled, for the first time, an evaluation of the relative contributions to DNA binding of different regions of the enzyme.  We found that there are a minimum of four DNA-binding sites throughout the telomerase protein, and that together these enable telomerase to bind very tightly to telomeric DNA, explaining its ability to maintain contact with the telomere.

Since our technique is quantitative, we found that a region previously implicated by others in binding to telomeric DNA actually contributes only a small portion of the ability to bind DNA.  Our data also suggest that different DNA binding sites are used by the enzyme during different stages of the addition cycle, adding to the complexity of what is known about telomerase mechanisms.