S-phase checkpoint pathways stimulate the mobility of the retrovirus-like transposon Ty1

The mobility of the Tyl retrotransposon in the yeast Saccharomyces cerevisiae is restricted by a large collection of proteins that preserve the integrity of the genome during replication. Several of these repressors of Tyl transposition (Rtt)/genome caretakers are orthologs of mammalian retroviral restriction factors. In rtt/genome caretaker mutants, levels of Tyl cDNA and mobility are increased; however, the mechanisms underlying Tyl hypermobility in most rtt mutants are poorly characterized. Here, we show that either or both of two S-phase checkpoint pathways, the replication stress pathway and the DNA damage pathway, partially or strongly stimulate Tyl mobility in 19 rtt/genome caretaker mutants. In contrast, neither checkpoint pathway is required for Tyl hypermobility in two rtt mutants that are competent for genome maintenance. In rtt101 Delta mutants, hypermobility is stimulated through the DNA damage pathway components Rad9, Rad24, Mec1, Rad53, and Dun I but not Chk1. We provide evidence that Tyl cDNA is not the direct target of the DNA damage pathway in rtt101 Delta mutants; instead, levels of Tyl integrase and reverse transcriptase proteins, as well as reverse transcriptase activity, are significantly elevated. We propose that DNA lesions created in the absence of Rtt/genome caretakers trigger S-phase checkpoint pathways to stimulate Tyl reverse transcriptase activity.