22/DNA Polymerase δ
Errors in DNA sequence result from environmental factors or are committed by DNA polymerases during replication. If unchecked, these errors might accumulate genetic damage such that the cell could no longer function. Thus, DNA repair processes involve mechanisms for the excision of damaged sequences and the resynthesis and ligation of the proper sequence. In mammalian cells, this proofreading function rests with DNA polymerase (pol) δ, a heterodimer of a 50kDa subunit, which stimulates pol δ activity in the presence of PCNA (proliferating cell nuclear antigen) and a 125kDa catalytic subunit. The catalytic subunit has 3' to 5' exonuclease activity which distinguishes pol δ from pol α and pol β. Pol δ is also central to DNA replication where it functions in leading strand synthesis at the replication fork. The catalytic subunit is phosphorylated by G1 cyclin-dependent kinase-cyclin complexes and, via its N-terminal 249 amino acids, interacts with cdk2. However, phosphorylation has little or no effect on the activity of pol δ. Thus, DNA polymerase ä is essential for DNA replication and is unique in its ability to replace damaged sequences through the process of DNA excision repair.