RRC ID 53720
Author Tse L, Kang TM, Yuan J, Mihora D, Becket E, Maslowska KH, Schaaper RM, Miller JH.
Title Extreme dNTP pool changes and hypermutability in dcd ndk strains.
Journal Mutat. Res.
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.
Volume 784-785
Pages 16-24
Published 2016-2
DOI 10.1016/j.mrfmmm.2015.12.004
PII S0027-5107(15)30057-9
PMID 26789486
PMC PMC4753124
MeSH Cytidine Deaminase / genetics* Cytidine Deaminase / metabolism DNA-Directed RNA Polymerases Deoxyribonucleotides / genetics Deoxyribonucleotides / metabolism Escherichia coli / drug effects Escherichia coli / genetics* Escherichia coli / metabolism Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Mutation* Mutation Rate Nucleoside-Diphosphate Kinase / genetics* Nucleoside-Diphosphate Kinase / metabolism Thymidine / pharmacology
IF 2.011
Prokaryotes E. coli