Mechanism of damaged DNA mutation identified

January 7, 2014, The Korea Advanced Institute of Science and Technology (KAIST)
Figure 1. ATM marks the position of the broken DNA, with TCTP helping to facilitate this reaction. DNA (blue line) within the cell nucleus is coiled around the histone protein (green cylinder). When DNA is broken, ATM protein attaches a phosphate group (P). Multiple DNA repair protein recognizes the phosphate as a signal that requires repair and gathers at the site.

A team led by KAIST Department of Biological Sciences' Professor Kwang-wook Choi and Dr. Seong-tae Hong has successfully investigated the operational mechanism of the protein ATM (Ataxia telangiectasia mutated), an essential protein to the function of a crucial key enzyme that repairs the damaged DNA which stores biometric information. The results were published on December 19th in the Nature Communications online edition.

All , including humans, constantly strive to protect the information within their DNA from damages posed by number of factors, such as carbonized material in our daily food intake, radioactive materials such as radon emitting from the cement of the buildings or ultraviolet sunlight, which can cause cancer.

In order to keep the DNA information safe, the organisms are always carrying out complex and sophisticated DNA repair work, which involves the crucial DNA damage repair ATM. Consequently, a faulty ATM leads to higher risks of cancer.

Until now, academia predicted that the protein TCTP (Translationally controlled tumor protein) will play an important role in regulating the function of ATM. However, since the main researches regarding TCTP have only been conducted in cultured cells, it was unable to identify exactly what mechanisms TCTP employs to control ATM.

Figure 2. When the amount of TCTP protein is reduced, cells of the Drosophila eye are abnormally deformed by radiation. Scale bars = 200mm

A KAIST research team has determined that TCTP can combine with ATM, and that TCTP increases the enzymatic activity of ATM. In addition, Drosophilia, one of the most widely used model organisms for molecular genetics, has been used to determine that TCTP and ATM play a very important role in repairing the DNA damaged by radiation. This information has allowed the researchers to establish that TCTP plays essential roles in maintaining the DNA information in cell cultures, as well as higher organisms, and to provide specific and important clues to the regulation of ATM by TCTP.

Figure 4. When gene expressions of TCTP and ATM are reduced, large defects occurs in the normal development of the eye. (Left: normal Drosophilia eye, right: development-deficient eye)


Figure 3. When the amount of TCTP protein is reduced, the chromosomes of Drosophilia are easily broken by radiation. Scale bars = 10 mm.
Professor Kwang-wook Choi says, "[This research] demonstrates that basic research using Drosophilia can make important contributions to understanding the process of diseases, such as cancer, and to developing adequate treatment."

Explore further: Researchers exploit cancer's faulty defence mechanism

Related Stories

Researchers exploit cancer's faulty defence mechanism

June 13, 2013
Researchers in Germany have found a new way to exploit the differences between cancer cells and normal cells that could lead to new treatments.

Study finds missing piece of pediatric cancer puzzle

July 19, 2013
Most of the time, it takes decades of accumulating genetic errors for a tumor to develop. While this explains the general occurrence of cancer in adults, it leaves a gap in understanding of the cause of pediatric tumors.

Detector of DNA damage: Structure of a repair factor revealed

June 19, 2012
Double-stranded breaks in cellular DNA can trigger tumorigenesis. Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich, Germany, have determined the structure of a protein involved in the repair and signaling ...

Stem cell researchers move toward treatment for rare genetic nerve disease

May 10, 2013
(Medical Xpress)—UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have used induced pluripotent stem cells (iPSC) to advance disease-in-a-dish modeling of a rare genetic ...

Recommended for you

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.