Newly Found Protein Places A Limit On Telomere Length

Credit: Thomas Ried, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health

Researchers have discovered a protein called TZAP, which is in charge telomere trimming when telomeres get dangerously long

The gradual erosion of telomeres is a well established aspect of the aging process. Whether it's a cause or response is not yet fully understood, but short telomeres are bad news for cellular health. Recent work has also revealed that overly long ones might be bad news too, and may lead to genomic instability - leaving DNA more vulnerable to damage and mutation. Essentially there appears to be a telomere 'sweet spot' in which healthy division is possible and DNA is kept in a protected, capped state.

In line with these findings, researchers have unveiled a new protein named TZAP, which appears to perform an important role in telomere trimming. In germ cells, healthy telomeres are particularly important for producing health offspring, so it's perhaps unsurprising that the cell has evolved a mechanism of keeping overly enthusiastic telomerase from overextending telomeres beyond a desirable point.  TZAP appears to play a critical role in this process. 

"Telomeres represent the clock of a cell. You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore. This cellular clock needs to be finely tuned to allow sufficient cell divisions to develop differentiated tissues and maintain renewable tissues in our body and, at the same time, to limit the proliferation of cancerous cells"

The shelterin complex proteins were believed to be the only proteins that bound telomeres 

Imposing a telomere limit

Previous to this work, it was thought the only proteins that bind to telomeres are the proteins involved in the shelterin complex. This complex protects telomeres and also regulates telomerase activity. Curiously, long telomeres seem to have a reduced concentration of this shelterin complex. The team at the Scripps Research Institute found, much to their surprise, that another protein was preferentially binding to longer telomeres - triggering telomere snipping. There have been some fears that therapies aiming to boost telomerase activity and extend telomeres may overdo it, but this research raises some new questions. It's possible these existing mechanisms may provide somewhat of a safety net. 

"There is a protein complex that was found to localize specifically at chromosome ends, but since its discovery, no protein has been shown to specifically localize to telomeres. This study opens up a lot of new and exciting questions"


Read more at MedicalXpress