Inhibition of NHEJ repair by type II-A CRISPR-Cas systems in bacteria

• Published in: Nature communications Vol. 8; no. 1; pp. 2094 - 9
• Main Authors: Bernheim, Aude, Calvo-Villamañán, Alicia, Basier, Clovis, Cui, Lun, Rocha, Eduardo P. C., Touchon, Marie, Bikard, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.12.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/181/735; 631/326/4041; 631/337/1427/2191; Bacillus subtilis - genetics; Bacillus subtilis - metabolism; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; CRISPR; CRISPR-Associated Proteins - genetics; CRISPR-Associated Proteins - metabolism; CRISPR-Cas Systems - genetics; Deoxyribonucleic acid; DNA; DNA damage; DNA End-Joining Repair - genetics; DNA repair; Genome, Bacterial - genetics; Genomes; Homology; Humanities and Social Sciences; Immunity; Life Sciences; Microbiology and Parasitology; Molecular interactions; multidisciplinary; Non-homologous end joining; Repair; Science; Science (multidisciplinary); Streptococcus infections; Streptococcus pyogenes - genetics; Streptococcus pyogenes - metabolism; Streptococcus thermophilus - genetics; Streptococcus thermophilus - metabolism; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02350-1

Type II CRISPR-Cas systems introduce double-strand breaks into DNA of invading genetic material and use DNA fragments to acquire novel spacers during adaptation. These breaks can be the substrate of several DNA repair pathways, paving the way for interactions. We report that non-homologous end-joining (NHEJ) and type II-A CRISPR-Cas systems only co-occur once among 5563 fully sequenced prokaryotic genomes. We investigated experimentally the possible molecular interactions using the NHEJ pathway from Bacillus subtilis and the type II-A CRISPR-Cas systems from Streptococcus thermophilus and Streptococcus pyogenes . Our results suggest that the NHEJ system has no effect on CRISPR immunity. On the other hand, we provide evidence for the inhibition of NHEJ repair by the Csn2 protein. Our findings give insights on the complex interactions between CRISPR-Cas systems and repair mechanisms in bacteria, contributing to explain the scattered distribution of CRISPR-Cas systems in bacterial genome. The double-strand breaks generated by CRISPR-Cas systems are the target of multiple DNA repair pathways. Here the authors find incompatibility between NHEJ and type II-A CRISPR-Cas systems due to Csn2 mediated inhibition of end-joining.