Cancer cells, however, often regain the ability to produce telomerase, permitting them to replicate indefinitely. Though scientists have sought ways to inhibit this enzyme, a lack of detailed information on the enzymes structure has hindered progress.
Prior studies have shown that telomerase is made up of multiple protein components and a stretch of RNA that is used as a template to create the short DNA repeats that are added to the ends of chromosomes. In order for telomerase to function, the RNA and protein components of telomerase must interact to form a stable complex capable of DNA replication. This interaction occurs mainly on the so-called TRBD domain, which plays an essential role in complex formation and full assembly of the enzyme.
Studies show if you delete the TRBD domain from telomerase, the enzyme is inactive because it can no longer assemble with RNA, Skordalakes says. Without the RNA, the enzyme can no longer replicate telomeres.
To get a clear view of this interaction, Skordalakes and co-workers obtained the three-dimensional structure of TRBD using X-ray crystallography, a technique that analyzes the diffraction patterns of X-rays beamed at crystals of a molecule to determine the molecules atomic structure.
Their studies reveal that the TRBD domain is shaped like a boomerang, with a structural organization that leads to the formation of a narrow well-defined pocket on the surface of the protein that enables the enzyme to bind the single-stranded RNA used as a template for the DNA repeats.
|Contact: Franklin Hoke|
The Wistar Institute