17 DNA Replication Accessory Proteins

Abstract

INTRODUCTION
DNA replication requires the concerted action of many enzymes, as well as other protein and non-protein cofactors. The DNA, in preparation for DNA synthesis, has to become single-strand to serve as a template for the replicative DNA polymerases (pols). It is this form of the DNA that is especially prone to damage of any kind. Nature has provided a set of proteins that support the replicative pols in performing processive, accurate, and rapid DNA synthesis. Furthermore, such proteins also prevent damage to the transient single-strand (ss) DNA. These proteins are called DNA replication accessory proteins. The three best known are the proliferating cell nuclear antigen (PCNA), replication factor C (RF-C), and replication protein A (RP-A). In this chapter, we focus on these three protein classes and compare them to their selected counterparts in eukaryotic viruses. Additional replication proteins that also assist the proper function of pols, such as the 3′ → 5′ exonuclease, DNA primase, RNase H, 5′ → 3′ exonuclease, DNA helicases, DNA ligases, and DNA topoisomerases, are covered in various other chapters.

Early Discovery of Replication Accessory Proteins in Prokaryotes by Genetics and Defined In Vitro Replication Systems
Fifteen years ago it was realized that bacteriophages of Escherichia coli provide a window to understand the cellular events of DNA replication (Kornberg and Baker 1992). By using ssDNA from φX174, G4, and M13 as model replicons, the requirements for a ssDNA-binding protein (SSB) and a DNA synthesis complex were identified. The latter includes the pol III holoenzyme, which...