Ubiquitous environmental and endogenous genotoxic agents cause DNA lesions that can interfere with normal DNA metabolism including DNA replication, eventually resulting in mutations that lead to carcinogenesis and/or cell death. Cells possess repair mechanisms like nucleotide excision and base excision repair pathways to maintain the integrity of the genome. However, some types of lesions are repaired very inefficiently and others may not be recognized and repaired before the lesion-containing DNA undergoes DNA replication. To prevent acute cell death through arrested DNA replication at unrepaired lesions, cells have a mechanism, referred to as translesion synthesis (TLS), which allows DNA synthesis to proceed past lesions. TLS depends on the Y family of DNA polymerases (Lindahl and Wood 1999, Masutani et al. 2000, Yang 2014).