RNAi-based discrimination of exogenous DNA by mitotic heterochromatin in fission yeast

In eukaryotes, invasive exogenous (exo)DNAs, such as viral DNA and replicative plasmids, are rapidly lost from dividing cells. While many exoDNA-restricting mechanisms are known in prokaryotes, these are rarely conserved in eukaryotes, prompting the question of whether eukaryotes have evolved their own. Here, we show that fission yeast clusters exoDNA molecules through RNA interference (RNAi)-dependent heterochromatin deposition. While the mitotic kinase Aurora B dissociated heterochromatin, its activity was confined to chromosomes, stabilizing exoDNA clusters during mitosis, promoting the unequal partition of exoDNA at cell division, and facilitating its elimination from the cell population. We propose that fission yeast discriminates exoDNA from its own chromosomes, making it a model for studying cell-autonomous immunity in eukaryotes. Overall design: Analysis of small RNA in different experimental conditions.