Replicative DNA polymerase δ but not ε proofreads errors in Cis and in Trans

PLoS Genetics
Carrie L FloodGray F Crouse

Abstract

It is now well established that in yeast, and likely most eukaryotic organisms, initial DNA replication of the leading strand is by DNA polymerase ε and of the lagging strand by DNA polymerase δ. However, the role of Pol δ in replication of the leading strand is uncertain. In this work, we use a reporter system in Saccharomyces cerevisiae to measure mutation rates at specific base pairs in order to determine the effect of heterozygous or homozygous proofreading-defective mutants of either Pol ε or Pol δ in diploid strains. We find that wild-type Pol ε molecules cannot proofread errors created by proofreading-defective Pol ε molecules, whereas Pol δ can not only proofread errors created by proofreading-defective Pol δ molecules, but can also proofread errors created by Pol ε-defective molecules. These results suggest that any interruption in DNA synthesis on the leading strand is likely to result in completion by Pol δ and also explain the higher mutation rates observed in Pol δ-proofreading mutants compared to Pol ε-proofreading defective mutants. For strains reverting via AT→GC, TA→GC, CG→AT, and GC→AT mutations, we find in addition a strong effect of gene orientation on mutation rate in proofreading-defective strains and demo...Continue Reading

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A MorrisonA Sugino
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J SyväojaS Linn
Jan 1, 1991·Methods in Enzymology·F Sherman
Sep 21, 1990·Cell·A MorrisonA Sugino
Aug 1, 1995·Trends in Biochemical Sciences·A Sugino
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·I J Fijalkowska, R M Schaaper
Jul 1, 1996·Nucleic Acids Research·U GüldenerJ H Hegemann
Apr 18, 1997·The Journal of Biological Chemistry·M J LongleyP Modrich
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·M C Earley, G F Crouse
Aug 31, 2000·Annual Review of Biochemistry·T A Kunkel, K Bebenek
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y H JinD A Gordenin
Aug 2, 2001·Nature Biotechnology·F StoriciM A Resnick
Jun 14, 2002·Current Biology : CB·Claudia ColussiMargherita Bignami
Nov 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robert E GoldsbyBradley D Preston
Feb 20, 2003·Journal of Bacteriology·Jennifer Wyrzykowski, Michael R Volkert
May 3, 2003·Current Biology : CB·Youri I PavlovThomas A Kunkel
Jul 29, 2003·The Journal of Biological Chemistry·Polina V ShcherbakovaThomas A Kunkel
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nina Costantino, Donald L Court
Mar 24, 2004·Cell·Sean J Johnson, Lorena S Beese
Feb 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xue-Song WuChih-Chuan Liang
Apr 9, 2005·Critical Reviews in Biochemistry and Molecular Biology·Parie Garg, Peter M J Burgers
Jun 14, 2005·Mathematical Biosciences·Qi Zheng

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Citations

Jan 30, 2016·Critical Reviews in Biochemistry and Molecular Biology·Scott A LujanThomas A Kunkel
Dec 25, 2015·DNA Repair·Gray F Crouse
Apr 21, 2016·Nature Reviews. Molecular Cell Biology·Jessica S WilliamsThomas A Kunkel
May 18, 2016·Nucleic Acids Research·Kouji HirotaShunichi Takeda
Jun 4, 2016·Molecular Cell·Rais A Ganai, Erik Johansson
Mar 17, 2017·Annual Review of Biochemistry·Peter M J Burgers, Thomas A Kunkel
Feb 28, 2019·Journal of Molecular Modeling·M C FoleyA Boyke
Mar 4, 2018·Current Genetics·Anna Bębenek, Izabela Ziuzia-Graczyk
Apr 28, 2019·Genetics·Duyen T Bui, Joachim J Li
Jan 2, 2020·The Journal of Biological Chemistry·Mallory R SmithBret D Freudenthal
Sep 8, 2019·Current Genetics·Marta A GarbaczThomas A Kunkel
Sep 5, 2020·Critical Reviews in Biochemistry and Molecular Biology·Thomas A Guilliam, Joseph T P Yeeles
Aug 21, 2018·The Journal of Clinical Investigation·Thomas A Kunkel
Jan 24, 2019·Nature Communications·Xuanxuan XingPolina V Shcherbakova
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Chelsea R BulockPolina V Shcherbakova
Jan 25, 2021·The Journal of Biological Chemistry·Mallory R SmithBret D Freudenthal
Mar 26, 2021·Nucleic Acids Research·Mareike HerzogFabio Puddu

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Methods Mentioned

BETA
PCR

Software Mentioned

Salvador

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