Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered cellular process helps cells respond to DNA damage

30.01.2003


Biochemical mechanism may lead to new cancer prevention and treatment strategies



Scientists at St. Jude Children’s Research Hospital have discovered a novel biochemical process that plays a critical role in helping cells in the body respond to DNA damage, such as that caused by exposure to radiation, environmental toxins or free radicals.
The findings could lead to new approaches to prevent cancer, better ways to treat cancer and to the development of sensitive methods determining whether people have been exposed to radiation or environmental toxins, according to the researchers.

A report on this discovery, published in the current issue of the journal Nature, describes this critical early step in a cell’s response to DNA damage. This step, a chemical modification of an enzyme called ATM, allows the enzyme to initiate a series of events that ultimately halt the growth of a damaged cell and help the cell survive.



The finding is important because DNA damage caused by radiation and environmental toxins can lead to mutations or cell death, and can also contribute to the development of cancers.

Michael Kastan, M.D., Ph.D., chair of the Department of Hematology-Oncology at St. Jude and Christopher Bakkenist, Ph.D., also of St. Jude co-authored the research.

The St. Jude researchers found that ATM is activated by a signal from damaged DNA only seconds after the damage occurs. The activated ATM, in turn, activates other proteins by attaching a molecule called "phosphate" to them in a process called phosphorylation. This sets off a cascade of biochemical reactions that amplifies the initial ATM response.

Among the proteins phosphorylated by ATM are Brca1 and p53. It was already known that these proteins play important roles in preventing cancer, and that mutated forms of Brca1 and p53 are responsible for inherited cancers, such as familial breast cancer. The new St. Jude findings thus provide new insights into the way cells signal to both Brca1 and p53 following DNA damage.

The scientists are hopeful that they can use this information to improve therapy for many types of tumors.

"Because ATM is central to a cell’s response to irradiation, blocking its activation or activity might make virtually any type of tumor much more sensitive to radiation therapy," Kastan said. "The new molecular mechanisms identified here should allow us to achieve this aim by blocking ATM activity, which would make tumors more sensitive to radiation."

The St. Jude researchers also developed an antibody that specifically recognizes activated ATM, and thus identifies only those ATM molecules that are responding to DNA damage. "Our technique for identifying activated ATM is so sensitive that we’ve been able to show that it takes only a couple of breaks in the entire DNA of the cell to activate and initiate all of the cell’s response mechanisms," Kastan said.

The identification of these molecular mechanisms and the development of specific antibodies against activated ATM might also provide a very sensitive way to determine if cells in a person have been exposed to an agent or toxin that damages DNA, according to Kastan.

"Such an assay has many obvious potential uses," Kastan said, "including the assessment of exposure to dangerous agents in the environment." Another potential clinical benefit of these discoveries applies to cancer prevention. Since damage to the DNA appears to contribute to the vast majority of human cancers, enhancing the response of cells to DNA damage could reduce cancer development, Kastan noted. Therefore, the discovery of how ATM is activated could help guide the development of ways to improve cellular responses to DNA damage, including responses to oxidative stress that are either induced or natural.

"Based on the insights we’ve gained from our findings, we may be able to develop ways to activate ATM and thereby prevent or reduce the problems associated with DNA damage," Kastan said.



This work was supported by grants from the National Cancer Institute and National Institute of Environmental Health Sciences.

About St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for childhood catastrophic diseases. The hospital’s work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC).

ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children’s Research Hospital. Families without insurance are never asked to pay.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

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

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>