Protein Cdc13 has crucial role in maintaining and lengthening telomeres, links to preventing aging and possible cancer therapies - EurekAlert! (article link)
- Parent Category: News
19 Sep 2010
- Published: 19 September 2010
Researchers found that two copies of the protein bind together to form what is called a "dimer," and how that dimer physically interacts with DNA, regulating how enzymes called telomerases access and lengthen the telomeres.
- "Cdc13 has a crucial support role in maintaining and lengthening telomeres," -- "..telomere lengthening is one of the ways cancer cells obtain their immortality."
- they are investigating the potential of small molecule inhibitors to serve as viable therapeutics against cancer by blocking telomerase and their related proteins.
- When the researchers introduced mutations into Cdc13 that prevented the protein from forming a dimer, it caused the telomeres to shorten, which would hasten the demise of the yeast cells.
- When they created mutations that prevented Cdc13 dimers from binding to DNA, it had the effect of excessively lengthening telomeres, an act the researchers attribute to the notion that Cdc13 helps regulate the ability of DNA-replication enzymes to access telomeres.
Protein clamps tight to telomeres to help prevent aging ... and support cancer
According to Skordalakes, the discovery of the dimeric nature of Cdc13 sheds light into the core function of this protein, the recruitment of telomerase (which is also a dimer) to the telomeres.
Within the Cdc13 dimer are multiple sites that can bind to DNA with varying degrees of affinity.
This allows Cdc13 to straddle the DNA so that one section grips tightly to DNA, while another section – with a more relaxed grip – can bind nearer the tail end of the DNA strand and where telomerase binds.
This feature of Cdc13 also assists in recruiting telomerase, summoning the enzyme into place above the telomere.
When Cdc13 interacts with telomerase its weaker hand lets go of DNA, allowing the telomerase to access the telomere while the "strong hand" keeps the telomerase-Cdc13 complex firmly attached to the chromosome end.
"It effectively serves as both a protective placeholder and a means of guiding telomerase activity,"