Telomerase and DNA structures

The DNA located at telomeres appears to fold into a number of structures, which are different from the structure of DNA in the rest of the chromosome.  For example, telomeric DNA can bend into a four-stranded structure known as a G-quadruplex (whereas most DNA has only two strands).

It was previously thought that telomerase is unable to extend telomeres that are folded into G-quadruplexes; this folding of the telomere could be one way that the cell controls telomerase action.  In collaboration with Dr Michael Jarstfer at the University of North Carolina, USA, we have found that telomerase is indeed unable to extend a certain subclass of G-quadruplexes, unless the DNA spontaneously unfolds itself.  To our surprise, however, telomerase was able to bind to and extend a different subclass of this structure.  The telomerase that we used for these experiments was derived from our favourite model organism, a one-celled pond creature called Tetrahymena, which happens to have a lot of telomeres and abundant telomerase.  Our findings have implications for understanding how telomerase is regulated in a cell, as well as for the development of a class of cancer drugs based on G-quadruplex structures.