Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme That Mutates Antibodies Also Targets Cancer-Causing Gene

15.12.2008
Rockefeller University scientists have found that the same enzyme that enables an effective immune response is also responsible for the DNA breaks that cause lymphomas.

The human immune system is in a perpetual state of self-experimentation. It expertly mutates and shuffles the DNA of its own cells to evolve new defenses against the vast array of microbes that try to invade our bodies. But when the genetic experiment goes awry, the result can be a deadly cancer.

Now, Rockefeller University scientists have discovered that the same enzyme that enables the immune system’s defensive creativity is also responsible for a particular genetic malfunction -- a translocation of one piece of DNA to the wrong chromosome -- that causes Burkitt’s lymphoma. The findings, to be published in the December 12 edition of Cell, suggest the enzyme, called activation-induced deaminase (AID), is probably involved in a broader range of cancers as well.

“We strongly suspect that many or all of the translocations of human lymphomas in mature B cells are the product of this enzyme,” says Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology. “And there’s more and more data to show that it may be involved in other cancers as well. It’s been identified in stomach cancers, for instance.”

A very specific translocation causes Burkitt’s lymphoma, a cancer that plagues children in equatorial Africa. It involves a DNA break in an immune system antibody gene and the much more rare break in a cancer-promoting gene called c-myc. Previous work had shown that AID was responsible for breaking antibody genes but not c-myc. In fact, scientists thought a host of other factors might be involved in the c-myc break, but AID had been all but ruled out.

Despite the prior studies, Davide Robbiani, a research associate in Nussenzweig’s lab and a Leukemia and Lymphoma Society Fellow, believed AID was the culprit. To prove it, he and his colleagues started by deleting the promoter region of the c-myc oncogene, rendering the gene inactive, in a mutant line of mice. By looking for -- and not finding -- the specific translocation in these mice, he showed that c-myc had to be active in order for its DNA break to take place.

He then inserted a DNA tag into the mouse genome that allowed him to induce a break at the c-myc gene, which occurs only very rarely if left to its own devices. He found that his artificially created breaks were comparable in most every way to the breaks caused by AID, but when he looked for the translocation in mice that didn’t produce this enzyme, they were nowhere to be found.

“This is a definitive study,” says Nussenzweig, who is also a Howard Hughes Medical Institute investigator. “We now know AID is causing damage in other parts of the genome, not just in antibody genes.”

Because AID normally enables the genetic experimentation that’s critical to an effective immune response, shutting it down even to fight cancer is perilous. “As a general rule, you wouldn’t want to give an AID inhibitor to everyone because immune systems would not be working so well,” Nussenzweig says. Still, a pharmaceutical AID inhibitor, if developed, might prove useful in treating certain tumors that are expressions of this powerful gene mutator.

The next step is to figure out exactly how AID works and identify other genetic sites where AID is active. “We are now developing the tools to do exactly that,” Robbiani says.

Brett Norman | Newswise Science News
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>