It’s been known for a while that some bacteria produce proteins that can manipulate (turn on or off) the DNA of living cells. To find out which protein and how it works has been an area of intense research. Much of the significant work has been with plant disease bacteria, and now it appears that a final link, explaining how the protein binds to specific DNA locations, has been established.
The invading bacteria (in this case a plant pathogen, Xanthomonas) produces proteins (in this case called TAL, a Transcription Activator-Like effector) that bind to specific locations on DNA, and alters what the DNA produces. The result is usually harmful to the organism, but useful for the bacteria.
Adam Bogdanove, associate professor in plant pathology [Iowa State University, USA], was researching the molecular basis of bacterial diseases of rice when he and Matthew Moscou, a student in the bioinformatics and computation biology graduate program, discovered that the so-called TAL effector proteins injected into plant cells by strains of the bacterium Xanthomonas attach at specific locations to host DNA molecules.
Researchers had previously shown that these proteins bind host DNA and activate genes important for disease, or in some cases defense against the bacteria. But no one yet understood how different TAL effectors recognized different parts of the DNA in order to attach and turn on the different genes at those locations.
Through computer analyses, Bogdanove and Moscou discovered that pairs of amino acids distributed throughout a TAL effector protein each specify a particular nucleotide, one of the bases in DNA abbreviated as the letters G, A, T, or C. The complete set of these pairs directs the protein to a matching string of Gs, As, Ts, and Cs in the DNA.
“This simple relationship allows us to predict where a TAL effector will bind, and what genes it will activate. It also makes it likely that we can custom engineer TAL effectors to bind to virtually any DNA sequence,” says Bogdanove.
According to Bogdanove, being able to predict TAL effector binding sites will lead quickly to the identification of plant genes that are important in disease. Natural variants that lack these binding sites are a potential source of disease resistance.
The identification of a protein and the mechanism by which it attaches to specific nucleotides, opens the possibility of using that protein for gene-therapy and genetic studies that require turning specific genes on or off. Of course, this is one approach. A lot of lab work and time will tell how effective it is.