Fifty years ago, scientists experimenting with gamma
radiation to sterilize canned foods were surprised to find spoiled meat in cans zapped with what they thought were lethal levels of ionizing radiation (
IR). Inside the bulging cans, they discovered a strain of bacteria now called Deinococcus radiodurans. This extremely resilient microbe can endure 100 times the IR levels that kill other bacteria and levels 2,000 times higher than the lethal human dose.
Researchers investigating the nature of radiation toxicity long ago settled on DNA as its principal target. Within this framework, efforts to understand D. radioduranss resistance have focused on the mechanisms of DNA
repair, with each study revealing seemingly greater levels of efficiency. Surprisingly, this extremophile relies on a set of apparently universal DNA repair
proteins, raising an even bigger paradox: DNA repair and synthesis depends on proteins, but these proteins suffer radiation damage, too. And no matter how efficient DNA repair enzymes might be under normal conditions, its not clear how they manage to resurrect a radiation-shattered
genome if they are also damaged.
Over the past few years, several observations have challenged the DNA-centered view of IR toxicity. For one thing, the D. radiodurans genome, sequenced in 1999, revealed nothing clearly unusual about its DNA repair components. And it appears that bacteria at the opposite ends of resistance sustain about the same amount of DNA damage from a given IR dose, with many bacterial species succumbing to IR doses that cause very little DNA damage. Shewanella oneidensis, for example, cannot survive doses causing less than one double-strand DNA break per genome although it encodes DNA repair systems that appear more complex than those in D. radiodurans, which can weather the 100 double-strand breaks per genome caused by much higher doses just fine.
Might the hypothetical genes identified in the D. radiodurans genome encode proteins with novel repair functions? Or perhaps resistant bacteria can use standard DNA repair equipment in ways other organisms cannot. Or maybe theres something special in the way the microbe packages its chromosomes.
A 2004 study by Michael Daly et al. found that IR-resistant and IR-sensitive
cells had significantly different mineral concentrations, lending support to a role of
manganese and iron in recovery. The researchers showed that the most resistant cells contained about 300 times more manganese and three times less iron than the most sensitive cells. In a new study investigating the functional consequences of this disparity, Daly et al. show that high cytosolic manganese and low iron concentrations facilitate resistance by protecting proteins, but not DNA, from IR-induced oxidative damage. Their findings offer a novel perspective on the long-cryptic nature of D. radiodurans resistance, shifting the focus of toxicity and resistance away from DNA damage and repair toward a potent form of protein protection.
Exposing cells to IR generates a range of potentially harmful molecules called reactive oxygen species (ROS). When ROS accumulate faster than cellular scavengers can neutralize them, they cause oxidative stress and can kill cells. Hydroxyl radicals, one of the primary ROS products of irradiated water (the major component of cells), are particularly toxic to DNA, and can generate other ROS, including hydrogen peroxide and superoxide (a simple peroxyl radical).
High intracellular concentrations of manganese ions are known to alleviate oxidative stress in several bacterial species; these ions can interact with different ROS depending on their oxidation state and their binding with different molecules. Daly et al. reasoned manganese might affect ROS generation during irradiation. They first tested manganeses ability to scavenge hydroxyl and superoxide radicals to determine whether its activity protects DNA or proteins. Whereas hydroxyl radicals tar
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