Extreme dNTP pool changes and hypermutability in dcd ndk strains

Mutation Research
Lawrence TseJeffrey H Miller

Abstract

Cells lacking deoxycytidine deaminase (DCD) have been shown to have imbalances in the normal dNTP pools that lead to multiple phenotypes, including increased mutagenesis, increased sensitivity to oxidizing agents, and to a number of antibiotics. In particular, there is an increased dCTP pool, often accompanied by a decreased dTTP pool. In the work presented here, we show that double mutants of Escherichia coli lacking both DCD and NDK (nucleoside diphosphate kinase) have even more extreme imbalances of dNTPs than mutants lacking only one or the other of these enzymes. In particular, the dCTP pool rises to very high levels, exceeding even the cellular ATP level by several-fold. This increased level of dCTP, coupled with more modest changes in other dNTPs, results in exceptionally high mutation levels. The high mutation levels are attenuated by the addition of thymidine. The results corroborate the critical importance of controlling DNA precursor levels for promoting genome stability. We also show that the addition of certain exogenous nucleosides can influence replication errors in DCD-proficient strains that are deficient in mismatch repair.

References

Dec 1, 1976·European Journal of Biochemistry·M MeuthP Reichard
Oct 1, 1992·Molecular Biology of the Cell·L Sun, J A Fuchs
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J W Drake
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C G Cupples, J H Miller
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R M Schaaper
Sep 1, 1985·Somatic Cell and Molecular Genetics·G L WeinbergD W Martin
Nov 28, 1969·Journal of Molecular Biology·N C Brown, P Reichard
Sep 1, 1970·Bacteriological Reviews·G A O'Donovan, J Neuhard
Jan 1, 1982·Environmental Mutagenesis·B A Kunz
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·G WeinbergD W Martin
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·Q Lu, M Inouye
Jan 1, 1996·Annual Review of Biochemistry·P Modrich, R Lahue
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·I J FijalkowskaR M Schaaper
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·K A Datsenko, B L Wanner
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·M Maliszewska-TkaczykI J Fijalkowska
Oct 22, 2010·Nucleic Acids Research·Dinesh KumarAndrei Chabes
Nov 5, 2011·Critical Reviews in Biochemistry and Molecular Biology·Anders HoferBritt-Marie Sjöberg
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Stéphanie GonRobert P Fuchs
Aug 29, 2012·Molecular and Cellular Biology·Arancha SánchezPaul Russell
Sep 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Heewook LeePatricia L Foster
Dec 12, 2012·DNA Repair·Roel M Schaaper, Christopher K Mathews
Feb 26, 2013·DNA Repair·Luisa LauretiIvan Matic
Aug 15, 2013·Molecular Microbiology·Brandon L McKethan, Stephen Spiro
Oct 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Deepti Ahluwalia, Roel M Schaaper
Apr 1, 2015·Nucleic Acids Research·Katarzyna H MaslowskaRoel M Schaaper

❮ Previous
Next ❯

Citations

Jul 28, 2016·Journal of Bacteriology·Jocelyn AngJeffrey H Miller
Dec 5, 2018·Antimicrobial Agents and Chemotherapy·Sara D'SouzaJeffrey H Miller
Apr 7, 2020·Current Genetics·Indu Kapoor, Umesh Varshney
May 11, 2018·ACS Synthetic Biology·Valérie PezoPhilippe Marlière

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.