Revealing the Superpowers of PrimPol: rescuing replicating microsatellites

R‐loops are potentially mutagenic three‐stranded structures where RNA has hybridized to one strand of DNA and displaced the other, exposing ssDNA. Long repeated R‐loop‐forming sequences are known to cause genomic instability and are associated with disease. Šviković et al ( 2019 ) show that even short tandem (microsatellite) repeats, abundant in the vertebrate genome, do form R‐loops and present a barrier to replication. However, the replication fork can move past these short R‐loop‐forming repeats through the re‐priming action of primase–polymerase (PrimPol), thus avoiding the loss of epigenetic information or DNA damage. Graphical Abstract Recent work suggests that even short, physiological DNA triplet repeats may form replication‐threatening secondary structures in cells lacking the repriming activity of PrimPol.