Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system

Kirill A. Datsenko, Ksenia Pougach, Anton Tikhonov, Barry L. Wanner, Konstantin Severinov, Ekaterina Semenova

Research output: Contribution to journalArticle

303 Citations (Scopus)

Abstract

CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) is a small RNA-based adaptive prokaryotic immunity system that functions by acquisition of short fragments of DNA (mainly from foreign invaders such as viruses and plasmids) and subsequent destruction of DNA with sequences matching acquired fragments. Some mutations in foreign DNA that affect the match prevent CRISPR/Cas defensive function. Here we show that matching sequences that are no longer able to elicit defense, still guide the CRISPR/Cas acquisition machinery to foreign DNA, thus making the spacer acquisition process adaptive and leading to restoration of CRISPR/Cas-mediated protection. We present evidence suggesting that after initial recognition of partially matching foreign DNA, the CRISPR/Cas acquisition machinery moves along the DNA molecule, occasionally selecting fragments to be incorporated into the CRISPR locus. Our results explain how adaptive CRISPR/Cas immunity becomes specifically directed towards foreign DNA, allowing bacteria to efficiently counter individual viral mutants that avoid CRISPR/Cas defense.

Original languageEnglish (US)
Article number945
JournalNature communications
Volume3
DOIs
StatePublished - Aug 15 2012

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Clustered Regularly Interspaced Short Palindromic Repeats
Bacterial Genes
immunity
Adaptive Immunity
infectious diseases
genes
deoxyribonucleic acid
Genes
Data storage equipment
Infection
acquisition
machinery
fragments
DNA
plasmids
viruses
loci
mutations
restoration
spacers

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Datsenko, Kirill A. ; Pougach, Ksenia ; Tikhonov, Anton ; Wanner, Barry L. ; Severinov, Konstantin ; Semenova, Ekaterina. / Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system. In: Nature communications. 2012 ; Vol. 3.
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Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system. / Datsenko, Kirill A.; Pougach, Ksenia; Tikhonov, Anton; Wanner, Barry L.; Severinov, Konstantin; Semenova, Ekaterina.

In: Nature communications, Vol. 3, 945, 15.08.2012.

Research output: Contribution to journalArticle

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AU - Datsenko, Kirill A.

AU - Pougach, Ksenia

AU - Tikhonov, Anton

AU - Wanner, Barry L.

AU - Severinov, Konstantin

AU - Semenova, Ekaterina

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AB - CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) is a small RNA-based adaptive prokaryotic immunity system that functions by acquisition of short fragments of DNA (mainly from foreign invaders such as viruses and plasmids) and subsequent destruction of DNA with sequences matching acquired fragments. Some mutations in foreign DNA that affect the match prevent CRISPR/Cas defensive function. Here we show that matching sequences that are no longer able to elicit defense, still guide the CRISPR/Cas acquisition machinery to foreign DNA, thus making the spacer acquisition process adaptive and leading to restoration of CRISPR/Cas-mediated protection. We present evidence suggesting that after initial recognition of partially matching foreign DNA, the CRISPR/Cas acquisition machinery moves along the DNA molecule, occasionally selecting fragments to be incorporated into the CRISPR locus. Our results explain how adaptive CRISPR/Cas immunity becomes specifically directed towards foreign DNA, allowing bacteria to efficiently counter individual viral mutants that avoid CRISPR/Cas defense.

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