Bridge RNAs enable programmable recombination between target and donor DNA. IS110 insertion sequences, a family of minimal mobile genetic elements, produce a structured non-coding RNA that specifically binds to their encoded recombinase. This bridge RNA contains two internal loops that base-pair with target and donor DNA, allowing for sequence-specific recombination. The loops can be independently reprogrammed to direct DNA insertion, excision, and inversion. The IS110 bridge recombination system offers a unified mechanism for these three fundamental DNA rearrangements, expanding the diversity of nucleic-acid-guided systems beyond CRISPR and RNA interference. The bridge RNA enables precise DNA recombination by bridging the target and donor DNA molecules through direct base-pairing interactions. The system allows for modular reprogramming of target and donor recognition, enabling programmable DNA rearrangements. The study demonstrates that the bridge RNA can be expressed in trans, enabling efficient DNA recombination in E. coli. The system also allows for the precise targeting of genomic sites, with high specificity and tolerance for mismatches. The bridge RNA is a general feature of the IS110 family, with diverse structures and lengths across different subfamilies. The study provides insights into the mechanism of recombination and highlights the potential of bridge RNAs for genome engineering and design.Bridge RNAs enable programmable recombination between target and donor DNA. IS110 insertion sequences, a family of minimal mobile genetic elements, produce a structured non-coding RNA that specifically binds to their encoded recombinase. This bridge RNA contains two internal loops that base-pair with target and donor DNA, allowing for sequence-specific recombination. The loops can be independently reprogrammed to direct DNA insertion, excision, and inversion. The IS110 bridge recombination system offers a unified mechanism for these three fundamental DNA rearrangements, expanding the diversity of nucleic-acid-guided systems beyond CRISPR and RNA interference. The bridge RNA enables precise DNA recombination by bridging the target and donor DNA molecules through direct base-pairing interactions. The system allows for modular reprogramming of target and donor recognition, enabling programmable DNA rearrangements. The study demonstrates that the bridge RNA can be expressed in trans, enabling efficient DNA recombination in E. coli. The system also allows for the precise targeting of genomic sites, with high specificity and tolerance for mismatches. The bridge RNA is a general feature of the IS110 family, with diverse structures and lengths across different subfamilies. The study provides insights into the mechanism of recombination and highlights the potential of bridge RNAs for genome engineering and design.