Eukaryotic Y-Family Polymerases: A Biochemical And Structural Perspective

Classical DNA polymerases, which replicate DNA rapidly and with high fidelity, stall upon encountering DNA damage. Thus nonclassical polymerases, which have evolved to accommodate DNA damage, are necessary to overcome these replication blocks. These nonclassical polymerases mainly belong to the Y-family and replicate DNA slower and with lower fidelity than their classical counterparts. Y-family polymerases employ surprising strategies to incorporate nucleotides opposite DNA damage. These include the use of larger and less constrained active sites, the use of Hoogsteen base pairing, and the use of amino acid side chains as templates. Y-family polymerases also engage in protein-protein interactions that are important for their recruitment to stalled replication forks and the coordination of their activities on the DNA. These polymerases function within a dynamic network of protein-protein interactions that are mediated by intrinsically disordered regions of these enzymes. This review focuses on the biochemical and structural studies of the Y-family polymerases, which have provided clear insights into their function.