Nav: Home

Researchers discover cell mechanism that delays and repairs DNA damage that can lead to cancer

February 27, 2019

Researchers from the University of Copenhagen have identified a specific mechanism that protects our cells from natural DNA errors - an 'enemy within' - which could permanently damage our genetic code and lead to diseases such as cancer. The study has just been published in one of the most influential scientific journals, Nature Cell Biology.

Researchers from the University of Copenhagen have discovered a mechanism that gives human cells a chance to stop piling up mutations cells replicate and divide in the body. The discovery could prove to be very useful in the development of new treatments against diseases caused by changes in human DNA such as cancer.

To limit harmful changes in the genetic code that may lead to potential diseases, the cells in our body rely on a natural defense mechanism. The new study shows how specialised proteins engulf and protect the damaged DNA and 'escort' it until the damage can be repaired. The researchers discovered that this process relies on precise timing and meticulous control inside the cells.

'We have discovered a specific mechanism in human cells that delay propagation of DNA damage in successive generations of dividing cells. This discovery helps us understand how our bodies protect themselves from many types of cancer', says Professor Jiri Lukas, Head of the Chromosome Stability and Dynamics Group and Executive Director of the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen.

Defense against an enemy within

Cancer typically develops from cells with damaged DNA. It is well-known that tobacco smoke or ultraviolet light causes lung or skin cancer precisely due to their ability to damage DNA. However bad this may be, the hope in these environment-caused cancers is that we are aware of their origins and can thus dramatically reduce the risk simply by discarding cigarettes or shielding ourselves against excessive exposure to sunlight.

What is less known is that a more problematic source of DNA damage is normal cellular processes such as DNA replication. These cannot be avoided because they are inevitably in action every time cells divide. The scale of this problem is best illustrated by realizing that our bodies are made up by successive divisions of trillions of cells, all originating from a single fertilized egg. Every day, a quarter of a trillion cells in the adult human body continue to divide to replenish old or damaged tissue. Amongst the multitude of DNA damage incurred during each such cell division process, the most dangerous are those that can be passed on from mother cells to newly born daughter cells. This inherited DNA damage is the true 'enemy within' that cannot be simply avoided by changing one's lifestyle.

Heritable DNA damage as a source of cancer

The new discovery is a result of many years of work and is rooted in the finding made eight years ago by the same group (also published in Nature Cell Biology). In 2011, Jiri Lukas' group found that inherited DNA damage caused by problems during DNA replication is protected in specialised organelles (literally 'small organs'; in practice sub-cellular compartments with a specific function) called '53BP1 nuclear bodies.

In the new study, the researchers took advantage of their ability to label the 53BP1 nuclear bodies in living human cells using fluorescent dyes and then followed them under the microscope over several successive generations. This made it possible for the first time to observe the fate of inherited DNA damage directly from the time of generation in mother cells to their final destiny in daughter cells. It was a true tour-de-force, as tracking living cells under the microscope for many hours, even days is a very challenging task, which only a few laboratories in the world can do.

The researchers found that daughter cells are well equipped for the challenges of life and mobilise 53BP1 nuclear bodies to 'escort' the inherited DNA lesions to a very late stage of their division cycle when they become competent for one last attempt to repair inherited DNA lesions.

The researchers also found that the key molecular part of this 'repair toolkit' is an enzyme called RAD52, which as a result of this study now qualifies as a true member of the tumour suppressor family of proteins that guards our DNA against cancer-predisposing mutations.

"53BP1 nuclear bodies delay cell division in daughter cells in order to reach the only remaining time in their lifecycle when they can mend DNA lesions that their mother caused but could not fix. This second chance is vital because it is also the last one. We have predicted and then experimentally documented that a failure of this second chance converts the initially curable DNA damage to one that can no longer be fixed. Accumulation of such mishaps could lead to disease, including cancer", says Assistant Professor Kai John Neelsen of the Novo Nordisk Foundation Center for Protein Research.

This knowledge may prove vital in the improvement of cancer therapy. As many cancer drugs damage the DNA of rapidly dividing cancer cells, understanding the timing and mechanisms for repairing DNA is essential in developing new drugs and minimising the side effects of current treatments.

"Our work reveals unexpected ways in which cells deal with inherited DNA damage. With the identification of the key proteins driving this process, we have laid the foundation for investigations into potential therapeutic applications", says Postdoc Julian Spies of the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen.
-end-
Contact

PhD Kai John Neelsen at the Novo Nordisk Foundation Center for Protein Research.

Phone: (+45) 35 33 26 88

Communications Adviser Andreas Westergaard

Phone: (+45) 53 59 32 80.

University of Copenhagen The Faculty of Health and Medical Sciences

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.
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

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...