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Eukaryotic DNA Replication : DNA polymerases
At least five high-fidelity eukaryotic DNA pols have been identified and categorized on the basis of molecular weight, cellular location, sensitivity to inhibitors, and the templates or substrates on which they act. They are designated by Greek letters rather than by Roman numerals (Fig. 1).
Figure 1: Activities of eukaryotic DNA polymerases (pol). [Note: The asterisk (*) denotes 3′→5′ exonuclease activity.]
1. Pol α: Pol α is a multisubunit enzyme. One subunit has primase activity, which initiates strand synthesis on the leading strand and at the beginning of each Okazaki fragment on the lagging strand. The primase subunit synthesizes a short RNA primer that is extended by the 5′→3′ polymerase activity of pol α, generating a short piece of DNA. [Note: Pol α is also referred to as pol α/primase.]
2. Pol ε and pol δ: Pol ε is recruited to complete DNA synthesis on the leading strand, whereas pol δ elongates the Okazaki fragments of the lagging strand, each using 3′→5′ exonuclease activity to proofread the newly synthesized DNA. [Note: DNA pol ε associates with proliferating cell nuclear antigen (PCNA), a protein that serves as a sliding DNA clamp in much the same way the β subunits of DNA pol III do in E. coli, thus insuring high processivity.]
3. Pol β and pol γ: Pol β is involved in gap filling in DNA repair. Pol γ replicates mitochondrial DNA.
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