Thursday, November 07, 2013

A microbe which reproduces without origins of replication

Every cell needs to copy its DNA before it divided, but the mechanisms by which this is accomplished are very different between the different domains of life. DNA copying begins at so-called origins of replication,  special DNA sequence which are chemically a bit easier to pry open and also recognized by the proteins responsible for initiating the replication process. Bacteria usually have one such origin per genome, while most archaea and all eukaryotes have multiple such origins.

But a paper in this week's Nature shows that at least some archaea, when deprived of DNA origins of replication, can still copy their genomes and continue dividing. The researchers were interested in the archeal microbe Haloferax Volcanii,  because the proteins it uses to replicate its genome are very similar to those of eukaryotes (including humans). When they generated a mutant strain of Haloferax which lacked all of the origins of replication, they were very surprised to see that these origin-less bugs continued to divide-- in fact at a slightly higher rate than the normal control bugs.

How could this be? It turns out that there are other ways to copy DNA, one of which, the DNA repair pathway, adds small stretches of DNA to patch DNA breaks.  Viruses such as papillomaviruses exploit this pathway to induce cells to make many copies of the viral DNA. In brief, the viral DNA is sensed by the cell as a broken DNA piece, and the repair enzymes trying to patch it end up copying it.
It turns out that the origin-deficient  Haloferax were using this same pathway to kludge a replication strategy without DNA damage.

Now, it turns out that the choice to study Haloferax may have fortuitously made detection of this surprising end-run mechanism easier. The natural environment of Haloferax are extremely saline regions such as the Dead Sea, and the biofilms are subjected to extreme temperature fluctuations and dessication, both of which naturally cause extensive DNA damage. Thus this archeon is naturally primed to have an active DNA repair kit.




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