Arrested replication forks guide retrotransposon integration

Long Terminal Repeat (LTR) Retrotransposons are an abundant class of genomic parasites that replicate by insertion of new copies into the host genome. LTR retrotransposons prevent mutagenic insertions through diverse targeting mechanisms that avoid coding sequences, but a universal set of principles guiding their target site selection hasn’t been established. Here we show that insertion of the fission yeast LTR retrotransposon Tf1 is guided by the DNA binding protein Sap1, and that the efficiency and location of the targeting depend on the activity of Sap1 as a replication fork barrier. We propose that Sap1 guides insertion of Tf1 by blocking the progression of the replication fork, and that the Tf1 transposon uses features of arrested forks to insert into the host genome. These observations point to a universal mechanism for determination of LTR retrotransposon target site selection. Overall design: High throughput sequencing of Tf1 insertions