Nav: Home

Scientists zoom in to watch DNA code being read

January 17, 2018

  • Extraordinary images show one of fundamental processes of life
  • Mechanism goes into overdrive in cancer - and could be target for new drugs
Scientists have unveiled incredible images of how the DNA code is read and interpreted - revealing new detail about one of the fundamental processes of life.

The mechanism for reading DNA and decoding it to build proteins for their needs is common to all animals and plants, and is often hijacked by cancer.

Researchers used an advanced form of electron microscopy called Cryo-EM, for which the Nobel Prize in Chemistry was awarded in 2017, to zoom in and capture images of the reading mechanism in unprecedented detail.

The discovery of exactly how the molecular mechanism works - published in the journal Nature - could open up new approaches to cancer treatment.

Scientists at The Institute of Cancer Research, London, captured images of molecular machinery called RNA Polymerase III in the act of transcribing a gene in exquisite and unprecedented detail.

The work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Cancer Research UK and the Wellcome Trust.

RNA polymerase III is crucial to life for all eukaryotic cells - including all animals and plants. In cancer, it is more active, causing cells to produce larger numbers of the building blocks they need to grow and multiply.

Cryo-EM is so powerful that it can take pictures of tiny molecules - approximately 5 nanometers or 20000th of the width of a human hair - at almost an atomic level.

It allowed researchers to see for the first time how components of the RNA polymerase III complex and accessory molecules interact and communicate with each other, suggesting how drugs might be employed to split the complex up.

The new study captured the molecular machinery in the act of binding to DNA, separating the two strands and getting ready to transcribe the DNA code.

Cryo-EM involves freezing and imaging samples at -180°C to preserve minute details of protein shapes. This type of microscopy is also an emerging and exciting approach in cancer drug design.

Scientists at The Institute of Cancer Research (ICR) used the technique to reveal five key stages in which the complex reshapes itself to successfully transcribe the DNA code. Each of these stages could potentially become the target of new cancer drugs.

The researchers looked at the molecular mechanism in yeast cells, but the same machinery is used in humans.

The complex reads the DNA code and makes material known as transfer RNA - an essential part of producing the protein building blocks needed to allow cells to grow or to make new cells.

Cancer cells need large numbers of these protein building blocks as they rapidly grow and divide, so they can become particularly reliant on components of the RNA polymerase III complex.

Dr Alessandro Vannini, Team Leader in Structural Biology at The Institute of Cancer Research, London, said:

"We used a really exciting new type of microscopy called Cryo-EM to do something no scientists have been able to do before. We were able to freeze and catch the RNA polymerase III complex in the act of attaching to, separating and reading the DNA code. We obtained almost a million of independent snapshots and, using powerful computers we grouped similar snapshots together, enhancing their detail to obtain a vivid reconstruction of this machinery at work."

"Now we know how the components of this crucial molecular mechanism fit together, we may be able to design drugs that turn the system on or off - and these could offer a whole new way of treating cancer."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"Cryo-EM is revolutionising molecular and cellular biology, allowing us to look in minute detail at molecular machines within cells and how they work. The technique is helping scientists to discover weaknesses in cancer cells that could be targeted by the next generation of drugs.

"This beautiful study has unveiled a fundamental cog in the inner workings of cells, and one that is often exploited by cancers. It's a hugely important finding in cell biology, and I hope that in future it will lead to new treatments for cancer patients."

Dr Amanda Collis, interim Executive Director of Science at BBSRC, said:

"Cryo-EM is rapidly advancing our knowledge of the structure and behaviour of biological molecules, and this exciting discovery demonstrates how fundamental understanding of biological systems can open the door to the development of potential new cancer therapies."

Universities and Science Minister Sam Gyimah said:

"This incredible new advancement in DNA decoding will further our understanding of disease, potentially leading to vital lifesaving treatment, including new ways to tackle cancer.

"The recently published Life Sciences Sector Deal, through our Industrial Strategy, will pave the way for more investment in innovative new treatments and technologies that will not only improve patient lives, but also drive economic growth making Britain fit for the future."
-end-
Images, animation and video are available on request.

For more information please contact Claire Hastings in the ICR press office on 020 7153 5380 or claire.hastings@icr.ac.uk. For enquiries out of hours, please call 07595 963 613.

Notes to editors

The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk

Institute of Cancer Research

Related Cancer Articles:

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.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

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

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".