Mutagenic cost of ribonucleotides in bacterial DNA

Proceedings of the National Academy of Sciences of the United States of America
Jeremy W SchroederLyle A Simmons

Abstract

Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context-dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repa...Continue Reading

References

Mar 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J NeuhardE Thomassen
Oct 1, 1991·Molecular & General Genetics : MGG·L Hansen, P von Wettstein-Knowles
Jul 14, 1989·Science·R S LahueP Modrich
Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Aug 31, 2000·Annual Review of Biochemistry·T A Kunkel, K Bebenek
Nov 1, 2003·The Journal of Biological Chemistry·Emmanuelle Le ChatelierLaurent Jannière
Nov 26, 2003·Molecular Cell·Jochen Genschel, Paul Modrich
Jun 15, 2005·Annual Review of Biochemistry·Aaron Johnson, Mike O'Donnell
Jul 28, 2005·Molecular Microbiology·Stéphane DuigouMarie-Françoise Noirot-Gros
Dec 27, 2005·Journal of Molecular Biology·Bethany E Dutra, Susan T Lovett
Aug 1, 2007·BMC Evolutionary Biology·Hiromi KochiwaAkio Kanai
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Stephanie A Nick McElhinnyThomas A Kunkel
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anna PluciennikPaul Modrich
Jan 14, 2011·Biochemistry·Jessica A Brown, Zucai Suo
Jun 28, 2011·Science·Nayun KimSue Jinks-Robertson
Aug 7, 2012·Molecular Cell·Justin L SparksPeter M Burgers
Jan 29, 2013·Nucleic Acids Research·Hyongi ChonSusana M Cerritelli
Apr 23, 2013·Molecular Cell·Scott A LujanThomas A Kunkel
Jul 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nina Y YaoMike E O'Donnell
Feb 6, 2014·Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis·Alexandra VaismanRoger Woodgate
Sep 8, 2015·Research in Microbiology·Justin S LenhartLyle A Simmons
Sep 19, 2015·Nucleic Acids Research·Monica C PillonAlba Guarné
Apr 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jochen GenschelPaul Modrich

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Citations

Nov 1, 2017·Journal of Bacteriology·Justin R RandallLyle A Simmons
Jan 24, 2019·Journal of Bacteriology·Justin R RandallLyle A Simmons
Sep 24, 2019·Nucleic Acids Research·Mary K JohnsonDeepak T Nair
Dec 17, 2019·The EMBO Journal·Michaela ŠikováLibor Krásný
Jan 20, 2021·Critical Reviews in Biochemistry and Molecular Biology·Zhi-Xiong ZhouThomas A Kunkel
Apr 7, 2021·Chembiochem : a European Journal of Chemical Biology·Sana OhashiHiroshi Abe

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Methods Mentioned

BETA
electrophoresis
PCR
Assay

Software Mentioned

R

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