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Monday, June 09, 2014

How Do Bacteria Survive Radiation Damage?

Secondary structure of the Trad_1400 gene (encoding a MutT hydrolase) in Truepera radiovictrix.
In the 1950s, a tin of meat was exposed to a dose of radiation that was thought to be capable of killing all known forms of life, but the meat subsequently spoiled, and Deinococcus radiodurans (dubbed Conan the Bacterium by some) was isolated from it. Various members of the Deinococcus-Thermus group have shown themselves to be incredibly hardy, able to survive extremes of temperature and doses of radiation that, frankly, they shouldn't be able to survive. (If any group of bacteria were able to survive space travel, this group surely could.)

Members of the Deinococcus group probably learned their DNA repair tricks very early in the history of terrestrial life, before there was sufficient oxygen in the atmosphere to support an ozone layer. In those times (before about one billion years ago), ultaviolet light from the sun would have been strong enough to sterilize almost any exposed surface. UV radiation, when it's strong enough, causes single- and double-strand breaks in DNA (just as ionizing radiation from radioisotopes or cosmic rays will). How Deinococcus manages to survive such radiation is still something of a mystery, although several repair modalities have been elucidated. We know that these bacteria have high copy numbers of their genetic material, and this no doubt facilitates repair. Still, double-stranded DNA breaks, in most organisms, are quickly fatal if they accumulate.

It turns out, DNA from Deinococcus-group bacteria is unusually rich in internal (intra-strand) complementarity, which means single strands of DNA are capable (in theory) of folding back on themselves to form elaborate secondary structures of high thermal stability. One such structure, for the Trad_1400 gene of Truepera radiovictrix (a radiation-tolerant member of the Deinococcus group), is shown above. This particular structure has a 37°C Gibbs free energy of minus-71.47 kcal/mol (meaning the structure is more likely to form than randomly coiled ssDNA) and a Tm (melting temperature) of 63.1°C, meaning it should be thermo-stable to around 145°F. Almost the entire gene folds back on itself; the only portion that doesn't self-anneal is the flat line on the bottom containing 29 bases.

If the (separated) strands of Truepera DNA can assume stable self-annealed structures of this type, it would go a long way toward explaining how the organism could survive double-stranded breaks. Fire a random bullet at the DNA and you're bound to hit secondary structure, not canonical (B-form) duplex DNA. A double-strand break in a stem structure might liberate a stem/loop from one strand, but the other strand could unfold to form a template for immediate repair of the damaged strand. Something like this is probably going on in radiation-resistant Deinococcus members, which have evolved to allow more than the usual secondary structure in their DNA.

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