Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Pinpoint New Role for Enzyme in DNA Repair, Kidney Cancer

10.06.2014

The discovery offers insights for the creation of better, more targeted therapies for various forms of cancer.

Twelve years ago, UNC School of Medicine researcher Brian Strahl, PhD, found that a protein called Set2 plays a role in how yeast genes are expressed – specifically how DNA gets transcribed into messenger RNA. Now his lab has found that Set2 is also a major player in DNA repair, a complicated and crucial process that can lead to the development of cancer cells if the repair goes wrong.


Max Englund, UNC Health Care

UNC researchers found that Set2 is needed for DNA repair. When mutated, the human version--SETD2--plays a role in kidney cancer.

“We found that if Set2 is mutated, DNA repair does not properly occur” said Strahl, professor of biochemistry and biophysics. “One consequence could be that if you have broken DNA, then loss of this enzyme could lead to downstream mutations from inefficient repair. We believe this finding helps explain why the human version of Set2 – which is called SETD2 – is frequently mutated in cancer.”

The finding, published online June 9 in the journal Nature Communications, is the first to show Set2’s role in DNA repair and paves the way for further inquiry and targeted approaches to treating cancer patients.

... more about:
»Cancer »DNA »Kidney »Medicine »Pinpoint »Set2 »UNC »modifications »proteins »repair

In previous studies, including recent genome sequencing of cancer patients, human SETD2 has been implicated in several cancer types, especially in renal cell carcinoma – the most common kind of kidney cancer. SETD2 plays such a critical role in DNA transcription and repair that Strahl is now teaming up with fellow UNC Lineberger Comprehensive Cancer Center members Stephen Frye, PhD, director of the UNC Center for Integrative Chemical Biology and Drug Discovery (CICBDD), Jian Jin, PhD, also with the CICBDD, and Kim Rathmell, MD, PhD, an associate professor in the department of genetics. Their hope is to find compounds that can selectively kill cells that lack SETD2. Such personalized medicine is a goal of cancer research at UNC and elsewhere.

In recent years, scientists have discovered the importance of how DNA is packaged inside nuclei. It is now thought that the “mis-regulation” of this packaging process can trigger carcinogenesis. This realm of research is called epigenetics, and at the heart of it is chromatin – the nucleic acids and proteins that package DNA to fit inside cells.

Proper packaging allows for proper DNA replication, prevents DNA damage, and controls how genes are expressed. Typically, various proteins tightly regulate how these complex processes happen, including how specific enzyme modifications occur during these processes. Some proteins are involved in turning “on” or turning “off” these modifications. For instance, protein and DNA modifications involved in gene expression in kidneys must at some point be turned off.

In 2002, Strahl found that Set2 in yeast played a role as an off switch in gene expression – particularly when DNA is copied to make RNA. Now, Strahl’s team found that Set2 also regulates how the broken strands of DNA – the most severe form of DNA damage in cells – are repaired. If DNA isn’t repaired correctly, then that can result in disastrous consequences for cells, one of them being increased mutation that can lead to cancer.

Through a series of biochemical and genetic experiments, Deepak Jha, a graduate student in Strahl’s lab, was able to see what happens when cells experience a break in the double-strand of DNA.

“We found that Set2 is required when cells decide how to repair the break in DNA,” said Jha, the first author of the Nature Communications paper. He said that the loss of Set2 keeps the chromatin in a more open state – not as compact as normal. This, Strahl said, leaves the DNA at greater risk of mutation. “This sort of genetic instability is a hallmark of cancer biology,” Jha said.

Strahl and Jha said they still don’t know the exact mechanism by which Set2 becomes mutated or why its mutation affects its function. But that’s the subject of their next inquiry. They are now collaborating with Rathmell and Ian Davis, also members of UNC Lineberger Comprehensive Cancer Center, to study how the human protein SETD2 is regulated and how its mutation contributes to cancer.

Strahl said, “We think this work will lead to a greater understanding of cancer biology, and open the door to future therapeutic approaches for patients in need of better treatment options.”

This research was funded through a grant from the National Institutes of Health.

Mark Derewicz | newswise
Further information:
http://www.unch.unc.edu

Further reports about: Cancer DNA Kidney Medicine Pinpoint Set2 UNC modifications proteins repair

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Stronger turbine blades with molybdenum silicides

26.09.2016 | Materials Sciences

Scientists Find Twisting 3-D Raceway for Electrons in Nanoscale Crystal Slices

26.09.2016 | Materials Sciences

Lowering the Heat Makes New Materials Possible While Saving Energy

26.09.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>