Discovery on How CRISPR Proteins Identify Targets

Researchers at University of California, Berkeley (UC Berkeley) have discovered how Cas1-Cas2, the proteins that allow the CRISPR immune system in bacteria to adapt to new viral infections, identify the site in the genome where they insert viral DNA so they can recognize it later and mount an attack. In the July 20 paper published in Science, Jennifer Doudna and her group reports capturing structures of Cas1-Cas2 in the act of inserting viral DNA into the CRISPR region. The structures revealed that a third protein, IHF, binds near the insertion site and bends the DNA into a U-shape, allowing Cas1-Cas2 to bind both parts of the DNA simultaneously. The team also discovered that the reaction requires that the target DNA bend and partly unwind, something that occurs only at the proper target.

CRISPR, the unique region of DNA where snippets of viral DNA are stored for future reference, allows the cell to recognize any virus that tries to re-infect. The viral DNA alternates with the "short palindromic repeats," which serve as the recognition signal to direct Cas1-Cas2 to add new viral sequences.

Specific recognition of these repeats by Cas1-Cas2 restricts integration of viral DNA to the CRISPR array, allowing it to be used for immunity and avoiding the potentially fatal effects of inserting viral DNA in the wrong place. This research opens the door for modification of the proteins themselves. Tweaking the proteins means that researchers might be able to redirect them to sequences other than the CRISPR repeat and expand their application into organisms without their own CRISPR locus.

For more details, read the UC Berkeley News.