Brothers-in-arms: How P53 and telomeres work together to stave off cancer

January 15, 2016

PHILADELPHIA--(Jan. 15, 2016) -- When it comes to genes associated with cancer, none have been studied more extensively than p53, a tumor suppressor gene that serves as the guardian of our genetic information. More than half of all cancers have mutations of p53, meaning that this particular gene must often be suppressed in order for a cancer to grow and spread.

P53 does not act alone in its protection of our genetic information. Telomeres - structures of proteins that cap off and protect our DNA at the tips of chromosomes like the aglets or clear tips of shoelaces - preserve these vital instructions as well. However, despite both p53 and telomeres offering similar benefits, the role of this key tumor suppressor gene as it relates to telomeres had never been properly described.

Now, new research from scientists at The Wistar Institute shows that p53 is able to suppress accumulated DNA damage at telomeres. This is the first time this particular function of p53 has ever been described and shows yet another benefit of this vital gene.

The findings were published in the European Molecular Biology Organization (EMBO) Journal.

The gene p53 regulates our genome's integrity. When DNA is damaged by cellular stress or other means, p53 helps to activate the transcription of genes that help with controlling the cell cycle and inducing apoptosis, or cell death. However, prior studies have shown that p53 can bind at many locations across the genome, including many sites that are not responsible for activating these regulatory genes, and p53 itself has many distinct binding sites. Since both p53 and telomeres protect the genome, Wistar's team wanted to focus on these binding sites to see how the two might be more closely related than has ever been shown.

"We believed that p53 may be responsible for a more direct protective effect in telomeres," said Paul Lieberman, Ph.D., professor and program leader of the Gene Expression and Regulation program, director of the Center for Chemical Biology and Translational Medicine, and the Hilary Koprowski, M.D., Endowed Professor at The Wistar Institute, and lead author of the study.

Using ChIP-sequencing, which allows researchers to study interactions between proteins and DNA, a team of scientists at Wistar identified p53-binding sites in subtelomeres. These are segments of DNA situated in between telomeres and chromatin, the complex of DNA and proteins found in the nucleus of our cells.

The researchers found that when p53 was bound to subtelomeres, the protein was able to suppress the formation of a histone modification called gamma-H2AX. This histone is modified in greater amounts when there is a double strand break on DNA. If it persists, the break is not repaired, so suppressing its expression means that the DNA is being preserved. Additionally, p53 was able to prevent DNA degradation in telomeres, thereby keeping them intact and allowing them to more properly protect the tips of our chromosomes.

"Based on our findings, we propose that the modifications to chromatin made by p53 enhance local DNA repair or protection," Lieberman said. "This would be yet another tumor suppressor function of p53, thus providing additional framework for just how important this gene is in protecting us from cancer."
This work was supported by the National Institutes of Health grants R01CA140652, F31CA174199, R01CA102184, R01CA164864, F31HG006395, R21 CA177395-01, and R21HG007205, with additional support provided by the Philadelphia Health Care Trust and the Commonwealth University Research Enhancement (CURE) Program from the Pennsylvania Department of Health. Core facilities support was provided by the Cancer Center Support Grant (CCSG) CA010815.

Other co-authors of this study from The Wistar Institute include Stephen Tutton, Greggory Azzam, Nicholas Strong, Olga Vladimirova, Andreas Wiedmer, Kate Beishline, Zhuo Wang, Zhong Deng, Harold Reithman, and Maureen Murphy. Other co-authors of the study include Jessica Monteith and Steven McMahon from Sidney Kimmel Medical College and Thomas Jefferson University in Philadelphia.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. On the Web at

The Wistar Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

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.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to