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Polymerase Switching in Response to DNA Damage

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Biophysics of DNA-Protein Interactions

Abstract

DNA polymerases are highly efficient and accurate macromolecular machines. They are capable of replicating DNA at up to 1,000 nucleotides per second while making less than one error in 100,000 additions. However, DNA is constantly subjected to damage from myriad sources. DNA damage disrupts normal cellular DNA replication by interfering with the accuracy and efficiency of replicative DNA polymerases. Specialized Y family DNA polymerases exist that can copy damaged DNA, although that ability often has a mutagenic cost. Therefore, Y family DNA polymerase activity is highly regulated in the cell. This chapter presents the functions of both replicative and Y family DNA polymerases and the cellular mechanisms of polymerase management. The focus is on Escherichia coli systems but also briefly discusses eukaryotic Y family polymerases. We first present DNA replication carried out by prokaryotic DNA polymerase III and describe its subunits and the coordination of leading and lagging strand replication. We then discuss DNA damage and specialized Y family DNA polymerases. Different models for the management of replicative and Y family DNA polymerases are presented. Finally, we briefly compare the eukaryotic systems with their prokaryotic counterparts.

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Acknowledgments

Research in the Beuning laboratory is supported by a New Faculty Award from the Camille & Henry Dreyfus Foundation and a CAREER Award from the NSF (MCB-0845033 to PJB). PJB is a Cottrell Scholar of the Research Corporation for Science Advancement. We thank Sebastian Zawiślak for assistance with the preparation of Figs. 11.6 and 11.8.

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Correspondence to Penny J. Beuning .

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Ollivierre, J.N., Silva, M.C., Sefcikova, J., Beuning, P.J. (2010). Polymerase Switching in Response to DNA Damage. In: Williams, M., Maher, L. (eds) Biophysics of DNA-Protein Interactions. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92808-1_11

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