DNA base damage is a major source of oncogenic mutations¹. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation². Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication^(3,4), we observe identical fidelity and damage tolerance for both strands. For small …