Beyond restricting viral replication, the ability of A3s to deaminate deoxycytidines in ssDNA have made A3s a double-edged sword. When overexpressed, A3s can mutate the host genome resulting in a variety of cancers. The identities and patterns of the mutations observed in cancer genomes can define the source of these mutations. Recently, the search for the deaminase(s) responsible for kataegic mutations found in breast cancer was narrowed down to APOBEC3B, through the comparison of all known APOBEC mutational signatures and eliminating APOBEC3G and other deaminases from potential mutational contributors9,13. Soon after, APOBEC3B was found to be correlated with a variety of other cancers such as ovarian, cervical, bladder lung, head and neck; signature sequence analysis was also a contributing factor that led to these conclusions14,15. Most recently APOBEC3H, which has a different sequence preference than APOBEC3B, has been identified to also play a role in breast and lung cancer16. Thus, defining A3 sequence specificity can be helpful in identifying A3s’ role in viral restriction and in cancer.