Fidelity consequences of the impaired interaction between DNA polymerase epsilon and the GINS complex

DNA Repair
Marta GarbaczIwona J Fijalkowska

Abstract

DNA polymerase epsilon interacts with the CMG (Cdc45-MCM-GINS) complex by Dpb2p, the non-catalytic subunit of DNA polymerase epsilon. It is postulated that CMG is responsible for targeting of Pol ɛ to the leading strand. We isolated a mutator dpb2-100 allele which encodes the mutant form of Dpb2p. We showed previously that Dpb2-100p has impaired interactions with Pol2p, the catalytic subunit of Pol ɛ. Here, we present that Dpb2-100p has strongly impaired interaction with the Psf1 and Psf3 subunits of the GINS complex. Our in vitro results suggest that while dpb2-100 does not alter Pol ɛ's biochemical properties including catalytic efficiency, processivity or proofreading activity - it moderately decreases the fidelity of DNA synthesis. As the in vitro results did not explain the strong in vivo mutator effect of the dpb2-100 allele we analyzed the mutation spectrum in vivo. The analysis of the mutation rates in the dpb2-100 mutant indicated an increased participation of the error-prone DNA polymerase zeta in replication. However, even in the absence of Pol ζ activity the presence of the dpb2-100 allele was mutagenic, indicating that a significant part of mutagenesis is Pol ζ-independent. A strong synergistic mutator effect obser...Continue Reading

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A MorrisonA Sugino
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J W Drake
Apr 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J D RobertsT A Kunkel
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J SyväojaS Linn
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·H ArakiA Sugino
Sep 21, 1990·Cell·A MorrisonA Sugino
Aug 1, 1995·Trends in Biochemical Sciences·A Sugino
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·T A KunkelK A Johnson
Jun 14, 1996·Science·J R NelsonD C Hinkle
Jul 19, 2002·The Journal of Biological Chemistry·Kikuo ShimizuAkio Sugino
Jan 2, 2003·DNA Repair·Christopher W Lawrence
Feb 7, 2003·The Journal of Biological Chemistry·Olga ChilkovaErik Johansson
Jun 14, 2003·TheScientificWorldJournal·Helmut Pospiech, Juhani E Syväoja
Nov 19, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Toshiaki TsubotaHisaji Maki
Mar 10, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tomoyuki FukuiShou Waga
Mar 19, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shin-Ichiro HiragaAkio Sugino
Apr 9, 2005·Critical Reviews in Biochemistry and Molecular Biology·Parie Garg, Peter M J Burgers
Jun 15, 2005·Annual Review of Biochemistry·Aaron Johnson, Mike O'Donnell
Jun 15, 2005·Annual Review of Biochemistry·Satya PrakashLouise Prakash
Dec 22, 2005·Nature Structural & Molecular Biology·Francisco J AsturiasErik Johansson
Mar 21, 2006·Trends in Biochemical Sciences·Miguel Garcia-Diaz, Thomas A Kunkel
Mar 21, 2006·Current Biology : CB·Tina M Albertson, Bradley D Preston
Sep 15, 2006·Nucleic Acids Research·Xuejun ZhongThomas A Kunkel
Jul 7, 2007·Science·Zachary F PursellThomas A Kunkel
Feb 16, 2008·Nucleic Acids Research·Amy L AbdulovicSue Jinks-Robertson
Apr 29, 2008·Molecular Cell·Stephanie A Nick McElhinnyThomas A Kunkel
May 13, 2008·Molecular Cell·Bruce Stillman
Oct 1, 2008·Trends in Cell Biology·Thomas A Kunkel, Peter M Burgers
Oct 7, 2008·The Journal of Biological Chemistry·Peter M J Burgers
Oct 18, 2008·The Journal of Biological Chemistry·Carrie M StithPeter M Burgers
Jun 24, 2009·Biochimica Et Biophysica Acta·Linda J Reha-Krantz
Aug 18, 2009·Mutation Research·Youri I Pavlov, Polina V Shcherbakova
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Stephanie A Nick McElhinnyThomas A Kunkel
Aug 24, 2010·Current Opinion in Cell Biology·Hiroyuki Araki
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andres A LarreaThomas A Kunkel

❮ Previous
Next ❯

Citations

Jan 30, 2016·Nature Reviews. Cancer·Emily RaynerDavid N Church
May 19, 2017·Current Genetics·Michał Dmowski, Iwona J Fijałkowska
Mar 4, 2018·Current Genetics·Anna Bębenek, Izabela Ziuzia-Graczyk
Apr 14, 2016·The Journal of Biological Chemistry·Joseph L StodolaPeter M Burgers
Jun 15, 2019·FEBS Letters·Kohji Hizume, Hiroyuki Araki
Jul 28, 2017·The Journal of Biological Chemistry·Andrey G BaranovskiyTahir H Tahirov
Aug 21, 2019·Critical Reviews in Biochemistry and Molecular Biology·David Gallo, Grant W Brown
Dec 17, 2020·International Journal of Molecular Sciences·Milena Denkiewicz-KrukIwona J Fijalkowska

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.