Resolution of a complex crisis at DNA 3′ termini

Ribonucleotides that are misincorporated into DNA during replication are removed by topoisomerase 1, which generates 3′-terminal adducts that are not amenable to DNA repair and thus compromise genome stability. A recent report by Li et al. reveals that Apn2/APE2 resolves such blocked 3′ termini, thereby suppressing topoisomerase 1–induced mutations at ribonucleotide monophosphate sites within the genome.