Molecular Biology

Polymerase Proofreader

See allHide authors and affiliations

Science  03 Jan 2014:
Vol. 343, Issue 6166, pp. 7
DOI: 10.1126/science.343.6166.7-c

For organisms to grow, and their cells divide, the genomes they contain must be replicated quickly and accurately. In eukaryotes, three DNA polymerases handle genome duplication: Pol α, which makes short RNA-DNA primers; Pol δ, which discontinuously replicates the lagging DNA strand and Pol ε, which replicates the leading strand, in a largely continuous and highly processive manner, unlike the other polymerases. Hogg et al. determine the 2.2 Å resolution crystal structure of the catalytic core of yeast Pol ε caught in the act of polymerization—bound to DNA and with an incoming dATP base. As well as the typical fingers, palm, thumb, exonuclease, and N-terminal domains, yeast Pol ε has a novel “P” domain that extends from the palm and encircles the DNA, embracing it as it leaves the active site. The P domain facilitates the high intrinsic processivity of Pol ε, independently of the processivity clamp protein, PCNA. It also extends the interactions between Pol ε and DNA by up to 10 nucleotides. Hogg et al. speculate that this much extended interface may contribute to Pol ε's high replication fidelity by allowing Pol ε to proofread the newly synthesized DNA for errors up to 45 Å from the active site.

Nat. Struct. Mol. Biol. 10.1038/nsmb.2712 (2013).

Navigate This Article