15 Cellular DNA Polymerases

Abstract

ENZYMATIC PROPERTIES AND CHARACTERISTICS THAT DISTINGUISH EACH DNA POLYMERASE
During the past decade, five DNA polymerases (pol) have been characterized in eukaryotic cells. These enzymes are called α, β, γ, δ and ɛ (Wang 1991). Their enzymatic properties, protein composition and structure, effectors, genetic relationships, genomic locations, expression during cell growth and proliferation, and their roles in DNA replication and repair have been described in previous reviews (Challberg and Kelly 1989; Stillman 1989, 1994; Hurwitz et al. 1990; Bambara and Jessee 1991; Wang 1991; So and Downey 1992). This chapter is an updated version of these reviews.

DNA pols α, β, δ, and ɛ are located in the nucleus, and DNA pol-γ is localized in the mitochondria. Therefore, pol-γ is thought to be the enzyme that replicates the mitochondrial DNA. The general enzymatic properties and characteristics that distinguish each DNA pol are summarized in Table 1, and the optimal assay conditions for each enzyme, such as pH, preferred primer template, and metal activators, are summarized in Table 2. The K_m values of their substrates and K_i values of their inhibitors vary widely depending on the purity of the enzyme, the integrity of the catalytic polypeptide, and the associated subunit components of the enzyme fraction used for the assay. Nonetheless, inhibitors can be used to distinguish one polymerase from another. Pols α, δ, and ɛ are sensitive to aphidicolin, but pols β and γ are not. Pols α, δ, and γ are sensitive to N-ethylmaleimide. Pol-α is particularly sensitive to...