Shifting replication between IInd, IIIrd, and IVth gears

摘要

We used to think cells could get by with just a few DNA polymerases. One processive polymerase in Escherichia coli [polymerase III (Pol III)] was needed to make the long trip around the genome, and another one (Pol I) was needed to replace Okazaki fragment primers or damaged nucleo-tides. This view changed radically after 2 seminal studies by Nelson, Lawrence, and Hinkle (1, 2) in which 2 yeast enzymes, Revl and Rev3-Rev7, were found to incorporate nucleosides or polymerize past template sites with missing or damaged bases. These new polymerases helped to explain a rich history of mutational phenomena and led to the realization that organisms have several of these specialized DNA polymerases; E. coli has 3 (Pol II, Pol IV, and Pol V). Yeast have 5. Humans have >10. Each appears specialized for polymerization through different structural classes of DNA damage (3). Although there is no shortage of polymerases from which to choose, the question of how and when they act in the cell has proved difficult to answer.