Nav: Home

New insight into how telomeres protect cells from premature senescence

June 30, 2017

Researchers at the Institute of Molecular Biology (IMB) and Johannes Gutenberg University Mainz (JGU) have further uncovered the secrets of telomeres, the caps that protect the ends of our chromosomes. They discovered that an RNA molecule called TERRA helps to ensure that very short (or broken) telomeres get fixed again. The work, which was recently published in the journal Cell, provides new insights into cellular processes that regulate cell senescence and survival in ageing and cancer.

Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from unravelling. Over a cell's lifetime, telomeres get gradually shorter with each cell division and therefore the protective cap becomes less and less effective. If they get too short, it is a signal for the cell that its genetic material is compromised and the cell stops dividing. Telomere shortening and reduced cell division are considered a hallmark of ageing and likely contribute to the ageing process. However, telomere shortening is also a defense mechanism against cancer because highly proliferative cells can only divide when their telomeres do not shorten. Therefore, telomere shortening is a double-edged sword and has to be carefully regulated to strike a balance between ageing and cancer prevention. When a telomere accidentally gets cut short early in a cell's lifetime, it needs to be fixed so that the cell doesn't become senescent too early.

"In the life of a cell, you have to find some sort of balance between cancer prevention and ageing. Telomeres are at the nexus between the two, so understanding how they are maintained is really important", said Brian Luke, Professor at the JGU Institute for Developmental Biology and Neurobiology and Adjunct Director at IMB.

Luke and his lab were interested in understanding how the cell recognizes these shortened and damaged telomeres that have lost their caps. Furthermore, they wanted to determine which factors were important for promoting the repair of short telomeres. This information could help in understanding why cells either commit to senescence or continue to grow.

In their recent paper, published in the prestigious journal Cell, Luke and his group have shown that one of the keys to understanding this problem is TERRA. TERRA is an RNA species that accumulates specifically at the ends of critically short telomeres by binding directly to the DNA and signals to the cell that these telomeres should be repaired, allowing the cell to carry on dividing.

"We already knew that short telomeres play a key role in determining the onset of cellular senescence, but we didn't really understand which features of short telomeres were important. What we have found with TERRA is an intricate regulatory system that explains how short telomeres are identified by the cell", said Luke.

The paper is actually the result of two different research projects on telomeres in the Luke lab. Diego Bonetti was looking into the regulation of TERRA in the cell cycle and found that TERRA levels were different at different stages of the cell cycle. Meanwhile, Arianna Lockhart and Marco Graf were investigating the accumulation of TERRA at short telomeres. When they discovered that the pattern of cyclic TERRA accumulation was different between short and long telomeres, they knew they were on to something and joined forces for this project.

Their joint work led them to realize that TERRA actually accumulates at all telomeres, but at long telomeres it is rapidly removed with the help of proteins Rat1 and RNase H2. These proteins bind preferentially to the long telomeres and ensure that TERRA is removed, but they are not present at the critically short telomeres, which means that TERRA remains for a longer time. This mechanism ensures the subsequent repair of the short telomere, which is crucial for the cell to survive and keep dividing.

Luke's work was carried out in yeast; however, telomeres and TERRA are found across all organisms with linear chromosomes. The researchers expect their work to be applicable to humans as well. Their next step will be to look into these processes in human cells and interrogate their implications for ageing and cancer.
-end-


Johannes Gutenberg Universitaet Mainz

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.