Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

09.07.2010
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:
http://www.mcmaster.ca

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>