14.3: Introduction

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Replication begins at one or more origins of replication along DNA, where helicase enzymes catalyze unwinding of the double helix. DNA unwinding creates replicating bubbles, or replicons, with replication forks at either end. Making a new DNA strand starts with making an RNA primer with RNA nucleotides and primase enzymes. DNA nucleotides are then added to the 3’-ends of primers by one a DNA polymerase. Later, other DNA polymerases catalyze removal of the RNA primers and replacement of the hydrolyzed ribonucleotides with new deoxyribonucleotides. Finally, DNA ligases stitch together the fragments of new DNA synthesized at the replication forks. This complex mechanism is common to the replication of ‘naked’ prokaryotic DNA and of chromatinencased eukaryotic DNA, and must therefore have arisen early in the evolution of replication biochemistry. In this chapter, we look at the details of replication and the differences in detail between prokaryotic and eukaryotic replication that arise because of differences in DNA packing. As with any complex process with many moving parts, replication is error-prone. Therefore, we will also look at how the overall fidelity of replication relies mechanisms of DNA repair that target specific kinds of replication mistakes, or mutations. At the same time, lest we think that uncorrected errors in replication are always a bad thing, they usually do not have bad outcomes. Instead, they leave behind the very mutations that allow natural selection and the evolution of diversity.

Learning Objectives

Explain how Cairns interpreted his theta (\(\Theta \)) images.
Compare and contrast the activities of enzymes required for replication.
Describe the order of events at an origin of replication and at each replication fork.
Compare unidirectional and bidirectional DNA synthesis from an origin of replication.
Outline the basic synthesis and proofreading functions of DNA polymerase.
Identify the major players and their roles in the initiation of replication.
Explain how Okazaki’s experimental results were not entirely consistent with how both strands of DNA replicate
List the major molecular players (enzymes, etc.) that elongate a growing DNA strand.
List the non-enzymatic players in replication and describe their functions.
Describe how the structure of telomerase enables proper replication.
Compare the activities of topoisomerases 1 and 2.
Explain the reasoning behind the hypothesis of processive replication.
Compare and contrast the impacts of germline and somatic mutations.
Describe common forms of DNA damage.
List enzymes of replication that were adapted to tasks of DNA repair.
Explain why a DNA glycosylase is useful in DNA repair.
Explain why the connection between 'breast cancer genes' and DNA repair.