Interactions Between Non Homologous End Joining Repair and Type II Crispr-Cas Systems

CRISPR-Cas systems confer bacteria and archaea an adaptative immunity against phages and other invading mobile genetic elements. Type II CRISPR-Cas systems target foreign DNA by generating double strands breaks, which can be repaired either by homologous recombination (template-based) or by Non Homologous End joining (NHEJ) that does not require any template. These systems will limit the efficiency of CRISPR-Cas systems if they repair the double strand breaks in invading DNA. The interference of homologous recombination in this process is expected to be negligible due to the lack of a template for repair. We therefore hypothesized that the NHEJ system could interfere with CRISPR immunity.  To test this idea, we used comparative genomics to study the interactions between CRISPR-Cas systems and NHEJ. We report a negative association between NHEJ and Type IIA CRISPR Cas systems.  We then investigated experimentally the possible molecular interactions causing this negative association. Our results suggest that NHEJ has no effect on CRISPR interference. However, the introduction of the Bacillus subtilis NHEJ system in Staphylococcus aureus abolished spacer acquisition by a Type IIA CRISPR-Cas system.Our findings give insights on the complex interactions between CRISPR-Cas systems and repair mechanisms in bacteria.