Products of bacteriophage T4 genes 32 and 45 improve the accuracy of DNA replication in vitro.

The six "accessory" proteins of the bacteriophage T4 specified by replication genes 32, 41, 44, 45, 61, and 62 were studied for their ability to enhance the accuracy with which phage T4 DNA polymerase (product of gene 43) replicates synthetic homopolymer duplexes in vitro. Two of these proteins, gene 32-protein (helix-destabilizing protein) and gene 45-protein, inhibited the selection of incorrect, but not correct, precursors, at the growing strand end. Gene 32-protein is shown to enhance replication fidelity by interacting with the DNA, whereas gene 45-protein exerts its fidelity-enhancing effect by interacting with the DNA polymerase. This is the first example to our knowledge of a DNA polymerase's accuracy being altered through interaction with another protein. Possible mechanisms by which gene 32- and gene 45-protein act to enhance replication fidelity are discussed.