Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Broken DNA Must Find Right Partners Quickly Amid Repairs

25.07.2008
A gene called ATM suppresses DNA break-induced chromosome translocations, which are present in some cancers and predict the success or failure of therapies for those cancers. The research, described in this week's issue of Nature, was performed at The University of Texas Health Science Center at San Antonio.

Just as square dance partners join hands at a particular point in the music, so broken pieces of DNA in our cells reunite as they are repaired. Precisely and quickly, these DNA pieces identify each other and tether together. A tumor-suppressor gene called ATM choreographs this fast-paced, but reliable, reassembly operation.

Sometimes the process goes awry. An ATM mutation predisposes children to cancers. In this week’s issue of Nature, researchers at The University of Texas Health Science Center at San Antonio describe this gene’s regulatory work more fully than ever before.

The paper, from the UT Health Science Center’s Institute of Biotechnology, is among the first to describe the molecular basis of chromosome translocations. These errors occur when genes from one chromosome glom onto another chromosome. Chromosomes are the tightly wrapped coils of DNA found in every cell.

... more about:
»ATM »Chromosome »DNA »proteins »translocation

Lead author Sang Eun Lee, Ph.D., associate professor of molecular medicine at the Health Science Center, suspected that chromosome translocations occur during DNA repair. DNA repair is the continuous process in which our genetic blueprint, or DNA, fixes damage caused by sunlight, diet, oxygen and chemicals that ding our DNA.

“This DNA repair process is usually highly accurate and reliable, but occasionally DNA makes the mistake of reshuffling or jumbling together material,” said Dr. Lee, a member of the Cancer Development and Progression Program of the Cancer Therapy & Research Center at the UT Health Science Center. “Translocations are found in many cancers, particularly leukemia. The presence of translocations predicts the success or failure of treatments for these cancers.”

Philadelphia chromosome-positive chronic myelogenous leukemia, a rare and aggressive cancer, involves translocation of genetic material from chromosomes 9 and 22, for example.

“The thing we haven’t understood is how chromosome translocations happen,” Dr. Lee said. “Our study recreated translocations in yeast cells. We monitored the translocation events in the context of DNA repair, which we believed to be the culprit.”

The researchers observed ATM-led machinery that prohibits chromosome translocations during DNA repair. ATM “traffic-controls” many other proteins, Dr. Lee said.

“When damage occurs, a chromosome, like thread, can be broken,” he said. “With exposure to radiation or other mutating agent, a chromosome may break in multiple places. Thankfully our DNA moves to repair this.”

Snippets of DNA, separated from adjacent snippets of the same chromosome, must reunite with them quickly. “Partner selections are very important, and we found that this selection occurs in a very short window of time,” Dr. Lee said. “We also observed the tethering together. Again, the gene central to all of this is ATM.”

The majority of children with ATM deficiency die at a young age from cancer. ATM mutation causes the disease ataxia telangiectsia.

“We were missing why ATM causes cancers,” Dr. Lee said. “Its strategic role in DNA repair, described in this paper, explains it.”

These observations may make it possible to tweak cellular machinery to prevent translocations and to develop anti-cancer drugs that bypass ATM deficiency by regulating gene proteins that interact with ATM.

Dr. Lee said information gleaned from the yeast cell experiments is extremely relevant to human cells “since the DNA repair mechanism is extremely well conserved across species.”

“Dr. Lee is following these chromosome events in real time during the repair process,” said Z. Dave Sharp, Ph.D., associate professor and interim chairman of the Department of Molecular Medicine at the Health Science Center. “The proteins he studied are in yeast, but these proteins carry out the same function in human cells. That’s the reason this paper is in Nature.”

The National Institutes of Health and the Leukemia Lymphoma Society funded the study. Members of Dr. Lee’s lab who worked on the project are Kihoon Lee, graduate student, and Yu Zhang, Ph.D., former graduate student.

About the UT Health Science Center San Antonio:

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit http://www.uthscsa.edu.

Will Sansom | Newswise Science News
Further information:
http://www.uthscsa.edu.

Further reports about: ATM Chromosome DNA proteins translocation

More articles from Life Sciences:

nachricht Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory

nachricht Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: ScanCut project completed: laser cutting enables more intricate plug connector designs

Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.

Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...

Im Focus: New Strategy Against Osteoporosis

An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.

Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...

Im Focus: AI & single-cell genomics

New software predicts cell fate

Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...

Im Focus: TU Graz Researchers synthesize nanoparticles tailored for special applications

“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.

Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...

Im Focus: Tailored light inspired by nature

An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.

Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“Conference on Laser Polishing – LaP 2020”: The final touches for surfaces

23.07.2020 | Event News

Conference radar for cybersecurity

21.07.2020 | Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

 
Latest News

Rare Earth Elements in Norwegian Fjords?

06.08.2020 | Earth Sciences

Anode material for safe batteries with a long cycle life

06.08.2020 | Power and Electrical Engineering

Turning carbon dioxide into liquid fuel

06.08.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>