This research article investigates how human cells integrate R2 retrotransposons into their genome through a process called PRINT. By utilizing high-content siRNA screening, the authors identified three distinct DNA repair pathways that host cells use to convert newly synthesized cDNA into stable genes. One pathway, mediated by Polθ, utilizes microhomology to join the DNA, while a second pathway involving 53BP1 and shieldin often results in truncated insertions. A third mechanism, dependent on CtIP and MRN, allows the DNA to anneal precisely with the target site. The researchers discovered that suppressing specific repair factors forces the system to produce only full-length, precise gene insertions. These findings enhance the potential for using retrotransposon-based tools in human gene therapy and genomic medicine.

References:

• McIntyre J J R, Horton C A, Collins K. Different repair pathways support intact or truncated insertions by R2 retrotransposon protein[J]. Science, 2025: eadz3121.