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Scientists have discovered new features of bacterial adaptive immunity

Russian scientists supervised by Professor Konstantin Severinov have found new features of CRISPR-Cas systems. This work’s results shed light on the old model of CRISPR-Cas system functioning.

“CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are key components of a system used by bacteria to defend against viruses. Cas – group of enzymes produced by the CRISPR-Cas system. CRISPR-Cas is the bacterial adaptive immune system. It provides acquired resistance against viruses. Bacteria pass it to the offspring. During the infection, a piece of viral DNA can be integrated into the bacterial genome (This procedure is called adaptation). Acquired DNA fragments (spacers) become a source of small CRISPR RNAs (crRNAs) programmed against DNA from which they originated. Foreign DNA is recognized and destroyed by a process called interferention.

photo credit: NAID

photo credit: NAID

But there is an evolutionary arms race between bacteria and their viruses. Viruses try to escape bacterial immunity and accumulate mutations in their genome; bacteria try to detect the modified viruses and destroy them. Due to this fact, specific version of spacer acquisition, referred to as “primed adaptation” takes place. Primed adaptation leads to selective acquisition of additional spacers from DNA which partially match the spacers in the genome. It provides stronger defense in the future. When the sequence in a CRISPR cassette fully matches a foreign DNA fragment (protospacer) — a target destruction without acquisition of additional spacers is observed. It was explained by structural differences in complexes formed on fully and partially matching targets. Scientists from Prof. Severinov lab have pointed out that this is not the case. They have showed that it is possible to modulate conditions when fully matching protospacers stimulate primed adaptation much more efficiently than partially matching ones. It is not observed in vivo due to the more rapid destruction of targets with fully matching protospacers. The spacer acquisition takes more time than destruction.

Deep understanding of CRISPR-Cas system work features is very important from both theoretical and practical points of view, because CRISPR-Cas is widely used in biotechnology as a very powerful tool for genome editing.

The results were published in prestigious journal PNAS.

* The Skolkovo Institute of Science and Technology (Skoltech) is a private graduate research university in Skolkovo, Russia, a suburb of Moscow. Established in 2011 in collaboration with MIT, Skoltech educates global leaders in innovation, advances scientific knowledge, and fosters new technologies to address critical issues facing Russia and the world. Applying international research and educational models, the university integrates the best Russian scientific traditions with twenty-first century entrepreneurship and innovation.

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