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Unrepaired DNA photodamage obstructs synthesis by replicative DNA polymerases. This blockage results in fork replication arrest, or the formation of gaps in the daughter strand, fragile structures that can lead to cell death. To protect the cells, they are equipped with the remarkable translesion synthesis (TLS) DNA polymerases that bypass the lesions. However, this replication may occur at the expense of DNA synthesis fidelity, causing mutations and tumorigenesis. Although these TLS DNA polymerases share many features, their roles in the cells differ according to the type of lesion, sequence context, and specific catalytic activity. This review mainly focuses on eukaryotic polymerases that are mostly studied and known to be involved in the bypass of ultraviolet (UV)-induced photodamage: the polymerases of the Y-family (Pol η, Pol ι, Pol κ and Rev1), Pol ζ of the B-family and PrimPol of the AEP-family. This chapter will discuss the particularities that make these TLS DNA polymerases bypass photoproducts. It will also discuss the mutagenic consequences, other functions for these polymerases, and the effects of protein oxidation by UVA-light on lesion bypass. In the end, we present some open questions for these remarkable enzymes to be investigated and discovered.

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