RNA and DNA Polymerases

Abstract

Transcription and replication in the living cell are among the most fundamental processes that constitute the essence of life. Replication of DNA is accomplished by DNA polymerases (DNAP) that synthesize exact copies of genomic DNA during cell division, while the expression of genetic information encoded in DNA is provided by cellular RNA polymerase (RNAP). Both kinds of enzymes perform the same type of reaction polymerization of nucleoside triphosphates (NTPs), suggesting similarities in their catalytic mechanisms. From a mechanistic point of view polymerases can be viewed as molecular machines that perform directional mechanical work against dissipative forces during polymerization. Such forces are hydrodynamic drag and impediments imposed by specific sequences encoded in DNA as well as by numerous proteins that hold on to DNA such as histones, regulatory factors and so forth. From this perspective both DNA and RNA polymerases can be compared with the other extensively studied molecular motors reviewed in the other chapters of this book such as myosins, kinesins, dyneins and bacterial flagellar motors. Some important mechanical and thermodynamic parameters of polymerases and other molecular motors are shown in Tab. 6.1. The interest in mechanical considerations of polymerases has been kindled by recent observations that the force generated by these enzymes greatly exceeds that of other known molecular motors. This consideration seems to be extremely useful since it means that general kinetic and thermodynamic concepts which were developed for more conventional molecular motors, can be applied to NTP polymerizing enzymes to better understand the mechanisms of DNA and RNA synthesis. Comparison of the properties of RNA and DNA polymerases reveals principal differences to kinesin-like motor proteins (Julicher and Bruinsma, 1998). These differences reflect the different purposes of these two kinds of enzymes: while motor proteins perform fast active transport in cells, the purpose of NTP polymer