Strand-biased cytosine deamination at the replication fork causes cytosine to thymine mutations in Escherichia coli

Proceedings of the National Academy of Sciences of the United States of America
Ashok S BhagwatPatricia L Foster

Abstract

The rate of cytosine deamination is much higher in single-stranded DNA (ssDNA) than in double-stranded DNA, and copying the resulting uracils causes C to T mutations. To study this phenomenon, the catalytic domain of APOBEC3G (A3G-CTD), an ssDNA-specific cytosine deaminase, was expressed in an Escherichia coli strain defective in uracil repair (ung mutant), and the mutations that accumulated over thousands of generations were determined by whole-genome sequencing. C:G to T:A transitions dominated, with significantly more cytosines mutated to thymine in the lagging-strand template (LGST) than in the leading-strand template (LDST). This strand bias was present in both repair-defective and repair-proficient cells and was strongest and highly significant in cells expressing A3G-CTD. These results show that the LGST is accessible to cellular cytosine deaminating agents, explains the well-known GC skew in microbial genomes, and suggests the APOBEC3 family of mutators may target the LGST in the human genome.

References

Jan 1, 1976·Progress in Nucleic Acid Research and Molecular Biology·H Hayatsu
Jun 1, 1978·Journal of Bacteriology·B K DuncanH R Warner
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S G GrantD Hanahan
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C T ChungR H Miller
Jul 30, 1974·Biochemistry·T Lindahl, B Nyberg
Jan 1, 1982·Annual Review of Biochemistry·T Lindahl
Mar 25, 1994·Nucleic Acids Research·J C ShenP A Jones
May 1, 1996·Molecular Biology and Evolution·J R Lobry
Jun 1, 1997·Trends in Genetics : TIG·M P Francino, H Ochman
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·M TangM F Goodman
Aug 4, 1999·Trends in Microbiology·S Karlin
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·K A Datsenko, B L Wanner
Jun 17, 2000·The EMBO Journal·C MasutaniF Hanaoka
Aug 10, 2000·Nature Structural Biology·S RaghunathanG Waksman
Jul 5, 2002·Nature·Svend K Petersen-MahrtMichael S Neuberger
Nov 28, 2002·Molecular Cell·Reuben S HarrisMichael S Neuberger
May 17, 2003·Science·Denise LecossierAllan J Hance
Jun 18, 2003·Cell·Reuben S HarrisMichael H Malim
Jun 9, 2004·Microbiology·Eduardo P C Rocha
Jun 15, 2005·Annual Review of Biochemistry·Satya PrakashLouise Prakash
Jun 28, 2005·Nucleic Acids Research·Christopher T WorkmanPanayiotis V Benos
Oct 13, 2005·Molecular Immunology·Igor B Rogozin, Youri I Pavlov
Jun 24, 2006·Methods in Enzymology·Patricia L Foster
Jul 22, 2006·Molecular Cell·Lance D Langston, Mike O'Donnell
Jun 15, 2007·Advances in Immunology·Silvestro G ConticelloMichael S Neuberger
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jared Nordman, Andrew Wright
Mar 27, 2010·DNA Repair·Michael A CarpenterAshok S Bhagwat
Mar 1, 2012·Chemical Reviews·Emil Paleček, Martin Bartošík
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
Sep 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Heewook LeePatricia L Foster
Mar 2, 2013·G3 : Genes - Genomes - Genetics·Patricia L FosterHaixu Tang

❮ Previous
Next ❯

Citations

Mar 30, 2016·Microbiome·David S Thaler
Sep 2, 2016·Chemical Reviews·Sachini U SiriwardenaAshok S Bhagwat
Dec 13, 2016·Genome Research·Vladimir B SeplyarskiyGeorgii A Bazykin
Nov 8, 2017·Critical Reviews in Biochemistry and Molecular Biology·Jeremy W SchroederJue D Wang
May 6, 2016·Journal of Virology·Brandy VerhalenMengxi Jiang
Oct 30, 2018·Genome Biology and Evolution·Nobuaki KonoKazuharu Arakawa
Mar 20, 2019·Scientific Reports·Mathilde NiocelAndrea Cimarelli
Dec 17, 2019·PLoS Genetics·Luis M CortezSteven A Roberts
Jul 4, 2019·Die Naturwissenschaften·Jacques Demongeot, Hervé Seligmann
Apr 23, 2017·Scientific Reports·Paweł BłażejPaweł Mackiewicz
Aug 5, 2020·Nature Genetics·David Mas-Ponte, Fran Supek
May 1, 2020·Frontiers in Microbiology·Aisha H SyedaChristian J Rudolph
Aug 7, 2019·Nature Communications·Joel C RosenbaumKara A Bernstein
Oct 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Artur A SerebrenikReuben S Harris
May 16, 2020·Frontiers in Microbiology·Ryudo OhbayashiShin-Ya Miyagishima
Mar 24, 2017·Nucleic Acids Research·James I HoopesSteven A Roberts
Dec 5, 2020·PLoS Computational Biology·Jennifer Lu, Steven L Salzberg
May 18, 2020·DNA Repair·Petria S Thompson, David Cortez
Mar 13, 2021·Nature Communications·Adam LangenbucherMichael S Lawrence
May 22, 2020·DNA Repair·Natalie Saini, Dmitry A Gordenin
May 1, 2021·International Journal of Molecular Sciences·Angéla BékésiBeáta G Vértessy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
A Beletskii, A S Bhagwat
Proceedings of the National Academy of Sciences of the United States of America
D A Kreutzer, J M Essigmann
© 2021 Meta ULC. All rights reserved