Triple Helix in Telomerase Structure Described
Telomerase is an enzyme that helps restore telomeres. Telomeres are little structures
at the end of DNA that have been linked to cell death and aging. When they 'wear out'
the DNA can no longer replicate properly, and the cell dies. Telomerase is not active
in most cells, so they age normally, but in cancer cells telomerase is active, giving
them their ability to continue dividing and growing.
Hence, telomeres and telomerase are important factors for understanding both aging
and cancer. While the molecular makeup of telomerase has been known for some years,
the physical structure is less well understood:
This is the first major piece of telomerase for which the structure is
known. Telomerase plays a key role in most cancers and possibly aging, and this work
ultimately may lead to targets for drug intervention, the scientists said.
Discovery of the structural makeup of a major part of this enzyme has already revealed
why certain mutations have devastating effects on the function of telomerase -- it changes
the shape:
The structure reveals a "pseudoknot" that is required for telomerase
activity, at whose core three strands of RNA come together to form a
triple helix. All vertebrate animals investigated so far have nearly
the identical sequence of nucleotides through the triple helix. So, for example
changing a single 'C' nucleotide to a 'U' nucleotide interferes with the folding of
the enzyme and causes aplastic anemia.
The persistence of this triple helix structure through all vertebrate evolution shows
that it must have an important function. Describing the structure and function of this
enzyme will help in understanding both how aging and cancers work, a necessary first step in
dealing with them.
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