Atomic Structure of the Herpes Simplex Virus 1 DNA Polymerase

Viral polynucleotide replication is central to the reproduction of all viruses. For DNA viruses, DNA polymerase is the core component of this process. There are at least six major DNA polymerase classes: class A, B, C, D, X, and Y (Koonin 2006, Burgers et al. 2001, Friedberg 2006). DNA replication in both bacterial and animal viruses is carried out by polymerases that belong to archaeal-class B DNA polymerases. These replicative polymerases also include the major eukaryotic DNA polymerases α, δ, ɛ, and also DNA polymerase ζ (Koonin 2006, Burgers et al. 2001, Friedberg 2006). The basic enzymatic function of a viral DNA polymerase is to catalyze the consecutive incorporation of new nucleotides to the 3′-end of the primer strand DNA using an existing single-strand DNA as the template (Lehman and Boehmer 1999, Knopf 1979, Boehmer and Villani 2003, Crute and Lehman 1989). For viral DNA replication to process faithfully, the structure of the polymerase must favor the incorporation of the correct nucleotides (Hwang et al. 1999, Chaudhuri et al. 2003). To further increase the fidelity of the process, many DNA polymerases possess a 3′–5′ exonuclease activity that removes the mismatched nucleotide from the primer DNA strand (Koonin 2006, Burgers et al. 2001, Friedberg 2006, Hwang et al. 1999, Gibbs et al. 1991, Song et al. 2004). There are also other functional proteins that assist replicative polymerases in their DNA replication process, these include helicase/primases that unwind double-strand DNA duplexes (Lehman And Boehmer 1999, Knopf 1979, Boehmer and Villani 2003, Crute and Lehman 1989, Marsden et al. 1997) and accessory factors that increase DNA polymerase processivity so that a single polymerase can elongate the primer strand by thousands of nucleotides before falling off the DNA duplex (Digard et al. 1993, Gottlieb et al. 1990, Parris et al. 1988, Weisshart et al. 1999, Chow and Coen 1995).