Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Seemingly suicidal stunt is normal rite of passage for immune cells

22.10.2008
Researchers have shown that self-induced breaks in the DNA of immune cells known as lymphocytes activate genes that cause the cells to travel from where they're made to where they help the body fight invaders.

Scientists have known for two decades or more that lymphocytes can break their own DNA in this fashion, creating splits in both of the two strands. However, the new finding is the first to link such serious damage to activation of genes not directly involved in the cells' attempts to either fix the harm or self-destruct to stop themselves from becoming cancerous.

When genes are activated is critical to the ability of cells to take on specialized roles in the body, and the finding, published online in Nature, left researchers wondering if other developmental pathways in different cell types are also triggered by DNA damage.

"It's also interesting to note that the cell sees the genetic material of some invaders, such as DNA viruses, as damaged DNA," says senior author Barry Sleckman, M.D., Ph.D, director of the Division of Laboratory and Genomic Medicine and an expert in DNA repair. "Could pathogens be taking advantage of these pathways outside of the previously recognized responses to DNA damage? We don't know yet."

The finding immediately improved scientists' understanding of ataxia telangiectasia, a rare genetic disorder that, among other symptoms, can weaken the immune system. Patients with the disorder have a mutation in a gene, ATM, that normally helps the cell sense DNA damage.

"This explains why the lymphocyte counts in these patients drop so sharply," Sleckman says. "Not only is the cell's ability to repair DNA damage slowed down, the lymphocytes can't activate the genes that get them to where they need to be."

Cells have built-in safeguards that regularly look for DNA damage. They can then repair it, or if that's not possible, push the cell to self-destruct. Both mechanisms help prevent DNA damage from turning a cell cancerous. For years, scientists assumed that a cell would view a break in both strands of DNA as serious damage and commit to self-destruction.

To their surprise, immunologists discovered two decades ago that breaking DNA was the source of one of the immune system's great strengths. Human DNA contains only 30,000 human genes, but the immune system makes proteins known as antibodies that recognize billions of different foreign substances. Immunologists showed that this was because lymphocytes create double-strand DNA breaks that allowed them to splice together their genetic materials in new ways. Material created from the new genetic combinations is used to generate antibodies and other defensive mechanisms that help the body defend itself against a much greater variety of invaders.

Sleckman wanted to examine the implications of DNA breaks in lymphocytes. In a cell line developed in his lab, researchers induced double-stranded breaks in lymphocyte DNA using the same enzymes the cells normally use to create the breaks. They then analyzed the genes activated as a result.

As expected, the breaks turned on two groups of genes: one, headed by the p53 protein, pushes the cell toward self-destruction; the other, headed by the NFKappa-B proteins, pushes for survival of the cell and repair of the damaged DNA. These groups of genes are normally activated in any cell that experiences DNA damage.

But Sleckman and his colleagues also found several lymphocyte-specific genes activated by the breaks.

"Several of these genes are involved in the migration and homing of lymphocytes," says Sleckman. "Lymphocytes are made in the bone marrow and the thymus, and they have to move to other niches, including the lymph glands, to do their work."

In addition to the young lymphocyte, scientists are aware of other instances where DNA is normally and regularly broken, such as the replication of DNA during cell division or the creation of reproductive cells like the sperm and the egg. Ionizing radiation and chemotherapy drugs also can cause similar damage to DNA. Finally, DNA strands from infectious agents that enter the cell can mimic damaged host DNA.

"It's entirely possible that some of these breaks are activating genetic mechanisms that are unrelated to DNA repair or cell survival, like the mechanisms we identified in lymphocytes," says Sleckman. "Understanding the broader scope of the cells' responses to DNA damage could potentially be important in a wide variety of contexts."

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>