8 Proofreading Exonucleases: Error Correction during DNA Replication

Abstract

I. INTRODUCTION
In elucidating the structure of DNA, Watson and Crick (1953a,b) proposed that during DNA replication, each strand could serve as a template for synthesizing its complementary partner strand, pairing A with T and G with C. They also suggested that spontaneous transition mutations might be accounted for by the presence of disfavored imino and enol base tautomers that could form A•C and G•T mispaired replication intermediates, stabilized by two and three H bonds, respectively. A large number of DNA synthesis fidelity studies have employed DNA polymerases purified from numerous prokaryotic and eukaryotic cellular and viral sources (for recent reviews, see Echols and Goodman 1991; Goodman et al. 1993). These in vitro fidelity studies have been complemented by physicochemical (Aboul-ela et al. 1985; Breslauer et al. 1986; Petruska et al. 1988; Gaffney and Jones 1989), nuclear magnetic resonance (Kan et al. 1983; Patel et al. 1984a,b; Sowers et al. 1986a,b, 1988a,b, 1989a,b), and X-ray (Brown et al. 1986Brown et al. 1989; Hunter et al. 1986a,b, 1987) structural studies using natural DNA and synthetic oligo-nucleotides containing matched and mismatched base pairs. “Stable” multiply H-bonded base mispairs in cationic (Sowers et al. 1986a,b), anionic (Driggers and Beattie 1988; Sowers et al. 1988, 1989a,b; Yu et al. 1993), and wobble structures (Kan et al. 1983; Patel et al. 1984b; Hunter et al. 1986a,b; Sowers et al. 1988, 1989a,b; Brown et al. 1989) have clearly been observed in B-form DNA, although the originally suggested disfavored tautomeric structures have not been detected.

DNA polymerases can catalyze...