Low fidelity DNA synthesis by a y family DNA polymerase due to misalignment in the active site.

The Journal of Biological Chemistry
Robert J KokoskaT A Kunkel

Abstract

Sulfolobus solfataricus DNA polymerase IV (Dpo4) is a member of the Y family of DNA polymerases whose crystal structure has recently been solved. As a model for other evolutionarily conserved Y family members that perform translesion DNA synthesis and have low fidelity, we describe here the base substitution and frameshift fidelity of DNA synthesis by Dpo4. Dpo4 generates all 12 base-base mismatches at high rates, 11 of which are similar to those of its human homolog, DNA polymerase kappa. This result is consistent with the Dpo4 structure, implying lower geometric selection for correct base pairs. Surprisingly, Dpo4 generates C.dCMP mismatches at an unusually high average rate and preferentially at cytosine flanked by 5'-template guanine. Dpo4 also has very low frameshift fidelity and frequently generates deletions of even noniterated nucleotides, especially cytosine flanked by a 5'-template guanine. Both unusual features of error specificity suggest that Dpo4 can incorporate dNTP precursors when two template nucleotides are present in the active site binding pocket. These results have implications for mutagenesis resulting from DNA synthesis by Y family polymerases.

References

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K Bebenek, T A Kunkel
Jul 11, 1990·Nucleic Acids Research·K A Eckert, T A Kunkel
Jan 1, 1995·Methods in Enzymology·K Bebenek, T A Kunkel
Jan 28, 1999·The Journal of Biological Chemistry·W P OsheroffT A Kunkel
Jul 10, 1999·Science·R E JohnsonL Prakash
Jan 5, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·T OgiH Ohmori
Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·R E JohnsonL Prakash
May 9, 2000·Nature·T MatsudaT A Kunkel
Sep 28, 2000·The Journal of Biological Chemistry·E OhashiT A Kunkel
May 29, 2001·The Journal of Biological Chemistry·R L LevineM Moriya
Aug 23, 2001·Molecular Cell·H OhmoriR Woodgate
Sep 14, 2001·Journal of Molecular Biology·T MatsudaT A Kunkel
Oct 31, 2001·Nature Structural Biology·L F SilvianT Ellenberger
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·P L Foster
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·K Bebenek, T A Kunkel

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Citations

Nov 1, 2003·Biochemical and Biophysical Research Communications·Patrick LestienneJacques Bonnet
Apr 28, 2004·Trends in Biotechnology·Andrey R PavlovAlexei I Slesarev
Jan 7, 1998·Cellular Signalling·A SchaeferH Marquardt
Jul 31, 2003·Mutation Research·Igor B Rogozin, Youri I Pavlov
Sep 9, 2010·Journal of the American Chemical Society·Meredith C FoleyTamar Schlick
Feb 7, 2012·The Journal of Physical Chemistry. B·Lai Man Chi, Sik Lok Lam
Jun 7, 2012·Chemical Research in Toxicology·Shanen M SherrerZucai Suo
May 15, 2010·The Journal of Biological Chemistry·James J FotiGraham C Walker
Jan 7, 2009·The Journal of Biological Chemistry·Shanen M SherrerZucai Suo
Jul 11, 2003·Nucleic Acids Research·Petr GrúzTakehiko Nohmi
Nov 21, 2007·Nucleic Acids Research·Jingyang ChenJoanne Stubbe
Feb 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Samuel Million-WeaverHoura Merrikh
Apr 15, 2008·Trends in Biochemical Sciences·Suse BroydeDinshaw J Patel
Sep 17, 2011·Chemistry & Biodiversity·Michael P StoneGanesh Shanmugam
Nov 28, 2013·The FEBS Journal·Mar Álvarez, Luis Menéndez-Arias
May 29, 2004·Trends in Microbiology·Brigette TippinMyron F Goodman
Aug 1, 2006·DNA Repair·Scott D McCulloch, Thomas A Kunkel
Mar 21, 2006·Trends in Biochemical Sciences·Miguel Garcia-Diaz, Thomas A Kunkel
Jun 10, 2004·Current Biology : CB·Oliver Fleck, Primo Schär
Aug 7, 2004·Structure·Sacha N UljonAneel K Aggarwal
Oct 21, 2006·Molecular Cell·Richard T PomerantzWilliam T McAllister
May 10, 2003·Structure·William A Beard, Samuel H Wilson

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