Lord of the Ring

01.05.2003

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Prof. Avi Minsky. The trick of survival
 
Solving a longstanding mystery, Weizmann Institute scientists have found what makes a certain bacterium the most radiation-resistant organism in the world. The microbe’s DNA is packed tightly in a unique ring-like structure, which keeps pieces of DNA broken by radiation in close enough proximity for repair to occur.
 
The red-colored bacterium Deinococcus radiodurans can withstand 1.5 million rads – 3,000 times more than humans. Its healthy appetite has made it a reliable worker at waste sites, where it eats up nuclear waste, transforming it into safer derivatives. The ability to withstand other extreme stresses, such as dehydration and low temperatures, makes the microbe one of the few life forms found on the North Pole. It’s not surprising, then, that it has been the source of much curiosity worldwide, with Russian scientists proposing that it originated on Mars, where radiation levels are higher.
 
DNA is the first part of a cell to be damaged by radiation. The most lethal damage is the breakage of both DNA strands. While most cells, including human cells, can mend only a few such breaks in their DNA, D. radiodurans can fix more than 200. This outstanding performance caused scientists to believe that the microbe must possess uniquely effective DNA repair enzymes; yet a series of experiments found that the microbe’s repair enzymes were very similar to those in ordinary bacteria.
 
Using an assortment of optical and electron microscopy methods, Prof. Avi Minsky of the Institute’s Organic Chemistry Department has now shown that the microbe’s resilience lies in the unique ring-like structure containing its DNA, which, following radiation damage, holds severed pieces of DNA closely together, allowing for repair. This is in contrast to most other organisms, where radiation breaks the DNA into fragments that float off into the cell’s liquids and are lost. 
 
“Exciting as these findings may be, I don’t expect them to boost the protection of humans from radiation. Our DNA is structured in a fundamentally different manner,” says Minsky. “The results may, however, lead to a better understanding of DNA protection in sperm cells, where a ring-like DNA structure has also been observed.”
 

More survival tricks

 

Minsky’s team also found that the microbe undergoes two phases of DNA repair. During the first phase the DNA repairs itself within the ring as described. It then performs an even more unusual stunt.
 
The bacterium is composed of four compartments, each containing one complete copy of DNA. Minsky’s group found two small passages between the compartments. After roughly 90 minutes of repair within the ring, the DNA unfolds and migrates to an adjacent compartment – where it mingles with the copy of DNA residing there. At this point, “regular” DNA repair enzymes, common in humans and bacteria alike, kick in. To complete the mending process, the enzymes compare the two copies of DNA, using each as a template to repair the other. 
 

…and a backup system

 

Their finding of a tightly packed ring made the team wonder how the bacterium manages its everyday tasks – including protein production, for which its DNA must first unfold. How, they asked, can the microbe do this if its DNA can barely budge? This question led to the uncovering of yet another of the microbe’s survival strategies: Of the four copies of DNA, there are always two (or sometimes three) tightly packed in a ring while the other copies are free to move about. Thus at any given moment, there are copies of DNA that drive protein production and others that are inactive but continuously protected.
 

Deinococcus radiodurans. rings give protection

D. radiodurans was discovered decades ago in canned food sterilized by using radiation – setting off questions as to how it could have survived. Though these questions have now been answered, the tide of speculation as to how these defense mechanisms evolved – and where – is likely to continue.
 
Minsky, along with other scientists, believes that the bacterium’s answer to acute stresses evolved on Earth in response to a harsh environment. The very same mechanism enabling it to fight dehydration and thus survive in some of the planet’s most inhospitable deserts also protects it from the destructive effects of radiation.
 
Prof. Abraham Minsky is the incumbent of the Professor T. Reichstein Professorial Chair. His research is supported by the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; TEVA Pharmaceutical Industries Ltd.; and the Verband der Chemischen Industrie.
 

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