Extended Data Fig. 10. Topoisomerase 1 causes small deletions while protecting against topological stress.

a, The canonical role of Topoisomerase 1 (TOP1) is to relieve torsional stress (sc, supercoiling) during replication and transcription. b, TOP1 acts by forming ssDNA nicks to release supercoils and then religates the relaxed DNA. However, TOP1 cleavage at genome-embedded ribonucleotides (frequently incorporated by replicative polymerases such as Pol ε), can lead to short deletions that will be most frequent at sites of torsional stress in the genome, such as occurs at highly transcribed genes. Adapted with permission from ref. ⁶, SpringerNature.