ABSTRACT
A block in DNA synthesis can have serious consequences for the cell. The recently discovered Y-family of DNA polymerases allows the cell to bypass specific lesions, which lead to a block for replicative polymerases and thereby permits cell survival (1). Y-family DNA polymerases replicate DNA in a distributive manner, which allows them to bypass the lesion, but ensures that a high-fidelity DNA polymerase is able to continue replication as soon as the block has been overcome. Despite the fact that these new enzymes are classified as DNA polymerases, they share little sequence homology to the five other DNA polymerase families, but have significant sequence homology within their family (Fig. 1) and contain five conserved sequence motifs, I-V (2). Additional residues mostly located towards the C-terminal end are highly variable and may be required for protein-protein interactions or other additional functions. Currently, the Y-family is divided into four subfamilies, which can be described as the 1. UmuC or pol V family that has only been identified in prokaryotes; 2. the Din B or pol IV family with members in bacteria, eukaryotes, and archaea presenting the most widely distributed family and the 3. Rev1 and 4. Rad30 families that are found exclusively in eukaryotes (2). All members of the Y-family lack a 30-50 exonuclease activity and are characterized as low-fidelity and low-processivity polymerases. Shortly after the identification of the Y-family of DNA polymerases, the first structures of members within this family were solved and currently two of the four subfamilies have been structurally characterized, (3-8) allowing the first detailed insight into their ability of lesion bypass and providing the structural basis of their low fidelity and processivity.
