DNA Helicases and DNA Motor Proteins
In recent years, a number of groundbreaking structural and mechanistic studies deepened our understanding of helicase mechanisms and established new approaches for their analyses. Many fundamental mechanistic questions ranging from the mechanism of force
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Helicases at the Replication Fork Peter McGlynn
Abstract Helicases are fundamental components of all replication complexes since unwinding of the double-stranded template to generate single-stranded DNA is essential to direct DNA synthesis by polymerases. However, helicases are also required in many other steps of DNA replication. Replicative helicases not only unwind the template DNA but also play key roles in regulating priming of DNA synthesis and coordination of leading and lagging strand DNA polymerases. Accessory helicases also aid replicative helicases in unwinding of the template strands in the presence of proteins bound to the DNA, minimising the risks posed by nucleoprotein complexes to continued fork movement. Helicases also play critical roles in Okazaki fragment processing in eukaryotes and may also be needed to minimise topological problems when replication forks converge. Thus fork movement, coordination of DNA synthesis, lagging strand maturation and termination of replication all depend on helicases. Moreover, if disaster strikes and a replication fork breaks down then reloading of the replication machinery is effected by helicases, at least in bacteria. This chapter describes how helicases function in these multiple steps at the fork and how DNA unwinding is coordinated with other catalytic processes to ensure efficient, high fidelity duplication of the genetic material in all organisms.
Introduction A need for enzymes that unwind double-stranded DNA into two single strands is perhaps most apparent during the process of DNA replication. A requirement to expose the bases within each strand for use as templates for DNA polymerases
P. McGlynn (*) Department of Biology, University of York, York, Yorkshire, UK e-mail: [email protected] M. Spies (ed.), DNA Helicases and DNA Motor Proteins, Advances in Experimental Medicine and Biology, DOI 10.1007/978-1-4614-5037-5_5, © Springer Science+Business Media New York 2013
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means that the entire genome of every cell must be unwound during every cell cycle. One requirement of replicative helicases is therefore very high processivity, enabling a single replication initiation event to result in synthesis of many thousands, perhaps millions, of base pairs. The central role of replicative helicases in genome duplication is also reflected in their functioning as moving platforms for the association of other components of the replisome, facilitating coordination of the multiple catalytic processes that must occur during both leading and lagging strand synthesis at the fork. However, recent years have uncovered many additional functions for other helicases at the replication fork. These additional functions are still emerging but include helicases that aid strand separation within the context of protein-bound DNA, processing of Okazaki fragments, convergence of replication forks and targeting of stalled forks to facilitate the reinitiation of DNA replication. Multiple roles for different helicases also imply exquisite coordination of thes
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