CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers

CRISPR-Cas immune systems in bacteria and archaea record prior infections as spacers within each system’s CRISPR arrays. Spacers are normally derived from invasive genetic material and direct the immune system to complementary targets as part of future infections. However, not all spacers appear to...

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Main Authors: Franziska Wimmer, Chase L. Beisel
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-01-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.03078/full
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author Franziska Wimmer
Chase L. Beisel
Chase L. Beisel
author_facet Franziska Wimmer
Chase L. Beisel
Chase L. Beisel
author_sort Franziska Wimmer
collection DOAJ
description CRISPR-Cas immune systems in bacteria and archaea record prior infections as spacers within each system’s CRISPR arrays. Spacers are normally derived from invasive genetic material and direct the immune system to complementary targets as part of future infections. However, not all spacers appear to be derived from foreign genetic material and instead can originate from the host genome. Their presence poses a paradox, as self-targeting spacers would be expected to induce an autoimmune response and cell death. In this review, we discuss the known frequency of self-targeting spacers in natural CRISPR-Cas systems, how these spacers can be incorporated into CRISPR arrays, and how the host can evade lethal attack. We also discuss how self-targeting spacers can become the basis for alternative functions performed by CRISPR-Cas systems that extend beyond adaptive immunity. Overall, the acquisition of genome-targeting spacers poses a substantial risk but can aid in the host’s evolution and potentially lead to or support new functionalities.
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spelling doaj.art-1ce97188a91f4771ae6a15e69bcb2afb2022-12-22T03:58:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-01-011010.3389/fmicb.2019.03078495190CRISPR-Cas Systems and the Paradox of Self-Targeting SpacersFranziska Wimmer0Chase L. Beisel1Chase L. Beisel2Helmholtz Institute for RNA-Based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyHelmholtz Institute for RNA-Based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyMedical Faculty, University of Würzburg, Würzburg, GermanyCRISPR-Cas immune systems in bacteria and archaea record prior infections as spacers within each system’s CRISPR arrays. Spacers are normally derived from invasive genetic material and direct the immune system to complementary targets as part of future infections. However, not all spacers appear to be derived from foreign genetic material and instead can originate from the host genome. Their presence poses a paradox, as self-targeting spacers would be expected to induce an autoimmune response and cell death. In this review, we discuss the known frequency of self-targeting spacers in natural CRISPR-Cas systems, how these spacers can be incorporated into CRISPR arrays, and how the host can evade lethal attack. We also discuss how self-targeting spacers can become the basis for alternative functions performed by CRISPR-Cas systems that extend beyond adaptive immunity. Overall, the acquisition of genome-targeting spacers poses a substantial risk but can aid in the host’s evolution and potentially lead to or support new functionalities.https://www.frontiersin.org/article/10.3389/fmicb.2019.03078/fullCRISPR-Casspacer acquisitionanti-CRISPR proteinsautoimmunitygene regulation
spellingShingle Franziska Wimmer
Chase L. Beisel
Chase L. Beisel
CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
Frontiers in Microbiology
CRISPR-Cas
spacer acquisition
anti-CRISPR proteins
autoimmunity
gene regulation
title CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
title_full CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
title_fullStr CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
title_full_unstemmed CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
title_short CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers
title_sort crispr cas systems and the paradox of self targeting spacers
topic CRISPR-Cas
spacer acquisition
anti-CRISPR proteins
autoimmunity
gene regulation
url https://www.frontiersin.org/article/10.3389/fmicb.2019.03078/full
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