Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


DNA discovery opens new door to develop tools, therapies for hereditary cancers

The finding is an important step forward in the field of molecular and structural biology

By solving the three-dimensional structure of a protein involved in repairing DNA errors, a group of McMaster University researchers have revealed new avenues to develop assessment tools and alternative treatments for people living with hereditary colorectal cancers.

The finding, published in the journal Molecular Cell, is an important step forward in the field of molecular and structural biology. The McMaster researchers uncovered how a specific protein, known as MutL, works within a cell to unleash the series of events that repair DNA when the replication machinery makes a mistake.

The research team was led by Alba Guarné, an associate professor in the Department of Biochemistry and Biomedical Sciences at McMaster, and involved researchers in Europe and the United States. The lead author of the study was Monica Pillon, a master's student in the Guarné laboratory.

Errors in DNA can arise from many types of damage including external harm, such as UV radiation or carcinogens, as well as by intrinsic cellular processes such as DNA replication. Failure to correct these errors leads to mutations, which results in cancer or a number of severe genetic disorders.

To prevent this from happening, cells posses a variety of DNA repair systems that correct these errors or trigger cell death when the damage cannot be fixed.

In this study, the investigators examined the DNA mismatch repair pathway, which corrects errors that have escaped proofreading during DNA replication. Specifically, they examined the protein MutL – a matchmaker protein – that recruits other enzymes and proteins within the cell to recognize, remove and correct mismatched DNA.

Research has shown that mutations on the genes that encode mismatch repair proteins give rise to two forms of familial cancer – hereditary non-polyposis colorectal cancer and Turcot Syndrome, which is associated with colorectal cancer as well as very aggressive brain tumours.

"The reason why it can lead to cancer is because if you don't have mismatch repair proteins that correct these errors, you're going to accumulate mutations," said Guarné. "People with defective mismatch repair genes develop cancers at very early ages. You would see a family that in their 30s has colorectal cancer and in their 40s they have it again. There's no way you can prevent that – you can't correct your DNA. As you grow older, you're going to accumulate mutations."

To determine how MutL is regulated, the researchers characterized the functional and structural domain of the protein that is involved in DNA mismatch repair. By mapping out MutL, they were able to unveil how the replication machinery turns MutL into an enzyme that cuts the error from the DNA. They also discovered that PCNA, another protein within the pathway, allows DNA to bind to MutL so it can be repaired.

"This is especially important because we've known for more than a decade that the PCNA protein is necessary to correct mismatches, but we didn't know its concrete function," Guarné said. "We're starting to understand that one of the roles of these replication proteins is to license the cutting activity of MutL."

The findings have profound implications in understanding the molecular mechanisms that predispose to cancer and Turcot syndrome development. In particular, it allows scientists to pinpoint mutations on the MutL protein in order to determine severity and long-term outcomes.

The results also provide new avenues to develop alternative cancer treatments, as the hope is future cancer therapies may be focused at the molecular level and involve blocking specific pathways within the cell.

The research was funded by the National Sciences and Engineering Research Council of Canada (NSERC) and the German Science Foundation.

The research appears in the July 9 print issue of Molecular Cell.

Veronica McGuire | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>