Double-strand DNA end-binding and sliding of the toroidal CRISPR-associated protein Csn2

Arslan, Zihni; Wurm, Reinhild; Brener, Oleksandr; Ellinger, P.; Nagel-Steger, Luitgard; Oesterhelt, Filipp; Schmitt, Lutz; Willbold, Dieter; Wagner, Rolf; Gohlke, Holger; Smits, Sander H. J.; Pul, Ümit

doi:10.1093/nar/gkt315

Cited by 43 publications

(46 citation statements)

References 65 publications

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“…Interestingly, though Cas9 information is important for Cas4, Cas1 is actually more significant for Csn2. This is in agreement with the hypothesized role of Csn2 in the adaptation process (42,43,44,45). An interesting case to consider is CasR, a helper protein of unclear function.…”

Section: Regression Instead Of Classification Learns Association Rulessupporting

confidence: 87%

CRISPRCasIdentifier: Machine learning for accurate identification and classification of CRISPR-Cas systems

Padilha

Alkhnbashi

Shah

et al. 2019

Preprint

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CRISPR-Cas genes are extraordinarily diverse and evolve rapidly when compared to other prokaryotic genes. With the rapid increase in newly sequenced archaeal and bacterial genomes, manual identification of CRISPR-Cas systems is no longer viable. Thus, an automated approach is required for advancing our understanding of the evolution and diversity of these systems, and for finding new candidates for genome engineering in eukaryotic models. In this paper, we introduce a holistic strategy that combines regression and classification models for improving the quality of protein cascades, predicting their subtypes, detecting signature genes and extracting potential rules that reveal functional modules for CRISPR.

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Section: Regression Instead Of Classification Learns Association Rulessupporting

confidence: 87%

CRISPRCasIdentifier: Machine learning for accurate identification and classification of CRISPR-Cas systems

Padilha

Alkhnbashi

Shah

et al. 2019

Preprint

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“…The CRISPR system is not well characterized in S. mutans, and the csn2 gene is found only in the type II-A systems. The Csn2 protein was recently characterized as forming a ring-shaped tetramer complex that binds to double-strand DNA ends with the proposed function of assisting in the integration of new spacer DNA fragments by stabilizing the DNA ends together and as a potential accessory protein recruiting DNA repair proteins (58). Perhaps increased csn2 gene expression contributes to ofloxacin tolerance by recruiting DNA repair proteins at the posttranscriptional level not detected in our microarrays.…”

Section: Discussionmentioning

confidence: 84%

The Formation of Streptococcus mutans Persisters Induced by the Quorum-Sensing Peptide Pheromone Is Affected by the LexA Regulator

et al. 2015

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bThe presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which these phenotypic variants are formed have been linked to stress response pathways in various bacterial species, but many of these mechanisms remain unclear. We have previously shown that in the cariogenic organism Streptococcus mutans, the quorumsensing peptide CSP (competence-stimulating peptide) pheromone was a stress-inducible alarmone that triggered an increased formation of multidrug-tolerant persisters. In this study, we characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed that in addition to exogenous CSP exposure, stressors, including heat shock, oxidative stress, and ofloxacin antibiotic, were capable of triggering expression of lexA in an autoregulatory manner akin to that of LexA-like transcriptional regulators. We demonstrated the role of LexA and its importance in regulating tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its involvement and regulatory role in the formation of persisters induced by the CSP-ComDE quorum-sensing regulatory system. We further identified key genes involved in sugar and amino acid metabolism, the clustered regularly interspaced short palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses that contribute to the formation of quorum-sensing-induced persister cells.T he classical view of bacterial survival against antibiotic killing has usually been seen as the expression of genetic resistance mechanisms that arise from mutations or gained through horizontal gene transfer. These resistance mechanisms include host target modification, degradation or modification of the antibiotic itself, and reduction in the permeability or increase in the efflux of the drug (1). A major survival mechanism of bacteria is antibiotic tolerance, whereby bacterial cells that have a slower or reduced growth rate become more tolerant toward antibiotic killing (2, 3). This reduction in bacterial growth is prominently perceived as one of the main survival mechanisms elicited in bacterial biofilms, by which the slower growth of biofilm cells contributes toward the highly recalcitrant nature of biofilm infections, even in biofilm populations that lack genetically encoded antibiotic resistance markers (4, 5).Formation of persister cells is the main factor responsible for the tolerance of pathogens to antibiotics. Persisters are nongrowing dormant cells that are produced in a clonal population of genetically identical cells. They constitute a small fraction of the bacterial population. Persisters are not mutants but phenotypic variants of the wildtype population (6). In contrast to the case with the aforementioned drug resistance mechanisms, which allow for bacterial cells to actively grow and divide unimpeded in the presence of specific antimicrobials, persisters are capable of sur...

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“…Several structural studies have revealed that Csn2 forms a tetrameric ring-shaped complex with a positively charged central cavity that binds to, and slides along, DNA fragments 39–43 . The apparent lack of Csn2 catalytic activity suggests that it might have an accessory role during spacer acquisition (such as stabilizing the double-strand break during spacer integration) or that it might be involved in the recruitment of additional factors 39 .…”

Section: Acquisition Of Spacersmentioning

confidence: 99%

Unravelling the structural and mechanistic basis of CRISPR–Cas systems

et al. 2014

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Bacteria and archaea have evolved sophisticated adaptive immune systems, known as CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems, which target and inactivate invading viruses and plasmids. Immunity is acquired by integrating short fragments of foreign DNA into CRISPR loci, and following transcription and processing of these loci, the CRISPR RNAs (crRNAs) guide the Cas proteins to complementary invading nucleic acid, which results in target interference. In this Review, we summarize the recent structural and biochemical insights that have been gained for the three major types of CRISPR–Cas systems, which together provide a detailed molecular understanding of the unique and conserved mechanisms of RNA-guided adaptive immunity in bacteria and archaea.

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Double-strand DNA end-binding and sliding of the toroidal CRISPR-associated protein Csn2

Cited by 43 publications

References 65 publications

CRISPRCasIdentifier: Machine learning for accurate identification and classification of CRISPR-Cas systems

CRISPRCasIdentifier: Machine learning for accurate identification and classification of CRISPR-Cas systems

The Formation of Streptococcus mutans Persisters Induced by the Quorum-Sensing Peptide Pheromone Is Affected by the LexA Regulator

Unravelling the structural and mechanistic basis of CRISPR–Cas systems

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