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5. DNA replication I: Enzymes and mechanism

A fundamental property of living organisms is their ability to reproduce. Bacteria and fungi can divide to produce daughter cells that are identical to the parental cells. Sexually reproducing organisms produce offspring that are similar to themselves. On a cellular level, this reproduction occurs by mitosis, the process by which a single parental cell divides to produce two identical daughter cells. In the germ line of sexually reproducing organisms, a parental cell with a diploid genome produces four germ cells with a haploid genome via a specialized process called meiosis. In both of these processes, the genetic material must be duplicated prior to cell division so that the daughter cells receive a full complement of the genetic information. Thus accurate and complete replication of the DNA is essential to the ability of a cell organism to reproduce.

In this chapter and the next, we will examine the process of replication. After describing the basic mechanism of DNA replication, we discuss the various techniques researchers have used to achieve a more complete understanding of replication. Indeed, a theme of this chapter is the combination of genetic and biochemical approaches that has allowed us to uncover the mechanism and physiology of DNA replication. In the remaining sections of the chapter, we focus on the enzymes that mediate DNA replication. In these descriptions, you will encounter several cases of structure suggesting a particular function. We will point out parallels and homologies between bacterial and eukaryotic replication components. This chapter covers the basic process and enzymology of DNA synthesis, and the next chapter will cover regulation of DNA replication.

Further readings

  • A. Kornberg and T. Baker (1992) DNA Replication, 2nd Edition, W.H. Freeman and Company, New York.
  • A. Kornberg, I. R. Lerman, M. J. Bessman, and E. S. Simms (1956) "Enzymic synthesis of deoxyribonucleic acid" Biochimica et Biophysica Acta 21:197-198.
  • M. Meselson and F. W. Stahl (1958) "The replication of DNA in Escherichia coli." Proceedings of the National Academy of Sciences, USA 44:671-682.
  • R. Okazaki, T. Okazaki, K. Sakabe, K. Sugimoto, and A. Sugino (1968) "Mechanism of DNA Chain Growth, I. Possible Discontinuity and Unusual Secondary Structure of Newly Synthesized Chains" Proceedings of the National Academy of Sciences, USA 59: 598-605.
  • P. De Lucia and J. Cairns (1969) Isolation of an E. colistrain with a mutation affecting DNA polymerase. Nature 224:1164-1166.
  • J. Gross and M. Gross (1969) Genetic analysis of an E. colistrain with a mutation affecting DNA polymerase. Nature 224:1166-1168
  • R. Sousa (1996) Trends in Biochemical Sciences 21:186-190. Similarities in structure among DNA polymerases
  • Herendeen and Kelly (1996) Cell 84:5-8.  Subunits and mechanism of DNA polymerase III.