CRISPR-Cas systems provide immunity to bacteria by programing Cas nucleases with RNA guides that recognize and cleave infecting viral genomes. Bacteria and their viruses each encode recombination systems that could repair the cleaved viral DNA. However, it is unknown whether and how these systems can affect CRISPR immunity. Bacteriophage λ uses the Red system (gam-exo-bet) to promote recombination between related phages. Here, we show that λ Red also mediates evasion of CRISPR-Cas targeting. Gam inhibits the host E. coli RecBCD recombination system, allowing recombination and repair of the cleaved DNA by phage Exo-Beta, which promotes the generation of mutations within the CRISPR target sequence. Red recombination is strikingly more efficient than the host’s RecBCD-RecA in the production of large numbers of phages that escape CRISPR targeting. These results reveal a role for Red-like systems in the protection of bacteriophages against sequence-specific nucleases, which may facilitate their spread across viral genomes.

CRISPR-Cas 系统通过使用识别和切割感染病毒基因组的 RNA 引导对 Cas 核酸酶进行编程来提供对细菌的免疫力。细菌和它们的病毒各自编码可以修复切割的病毒DNA的重组系统。然而，尚不清楚这些系统是否以及如何影响 CRISPR 免疫。噬菌体 λ 使用 Red 系统 ( gam - exo - bet ) 来促进相关噬菌体之间的重组。在这里，我们表明 λ Red 还介导了 CRISPR-Cas 靶向的规避。Gam 抑制宿主E。大肠杆菌RecBCD 重组系统，允许通过噬菌体 Exo-Beta 重组和修复切割的 DNA，从而促进 CRISPR 靶序列内突变的产生。在产生大量逃避 CRISPR 靶向的噬菌体方面，红色重组比宿主的 RecBCD-RecA 更有效。这些结果揭示了 Red 样系统在保护噬菌体免受序列特异性核酸酶侵害中的作用，这可能有助于它们在病毒基因组中的传播。