Eukaryotic DNA Polymerases

Abstract Deoxyribonucleic acid (DNA) is replicated and repaired by a family of enzymes called DNA polymerases. Eukaryotic cells have a diversity of these enzymes that, while sharing a common biochemical activity, are specialised for particular roles. Three polymerases are required for the replication of the nuclear genome, with Pol α involved in priming and initial synthesis and Pols δ and ϵ involved in bulk DNA replication. These polymerases are dependent on a large number of other proteins which unwind the DNA and perform other functions essential for efficient DNA synthesis. Polymerases are also involved in DNA repair and many repair‐specific enzymes have been identified. Some repair polymerases can refill a gap generated by removal of damaged DNA, or copy a damaged template, allowing DNA synthesis to proceed across a damaged template. Repair polymerases can also have tissue‐specific functions in lymphoid cells, where they contribute to somatic hypermutation of immunoglobulin genes. Key Concepts: Catalytic function of DNA polymerases. Concepts of ‘proofreading’ and ‘processivity’. Roles of replicative DNA polymerases needed for chromosome replication and organisation at the replication fork. Function of accessory proteins needed for polymerase function in chromosome replication. Different modes of action of specialised polymerases involved in DNA repair. Catalytic mechanism of polymerases. Assays used to detect polymerase function in vitro . Relevance of DNA polymerases to human disease.