The Spectrum of Replication Errors in the Absence of Error Correction Assayed Across the Whole Genome of Escherichia coli

When the DNA polymerase that replicates the chromosome, DNA polymerase III, makes an error, there are two primary defenses against mutation: proofreading by the ϵ subunit of the holoenzyme and mismatch repair. In proofreading-deficient strains, mismatch repair is partially saturated and the cell...

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Bibliographic Details
Published in:Genetics (Austin) 2018-08, Vol.209 (4), p.1043-1054
Main Authors: Niccum, Brittany A, Lee, Heewook, MohammedIsmail, Wazim, Tang, Haixu, Foster, Patricia L
Format: Article
Language:English
Subjects:
Accuracy
Bacteria
Base pairs
Deoxyribonucleic acid
DNA
DNA Damage
DNA Mismatch Repair
DNA polymerase
DNA Polymerase III - metabolism
DNA repair
DNA Replication
DNA, Bacterial - genetics
DNA-directed DNA polymerase
E coli
Editing
Error correction
Escherichia coli
Escherichia coli - genetics
Escherichia coli Proteins - metabolism
Experiments
Gene expression
Gene sequencing
Genetic recombination
Genetics
Genomes
Investigations
Load distribution
Mismatch repair
Mutagenesis
Mutation
Mutation Rate
Mutation rates
Proofreading
Repair
Replication
SOS response
SOS Response (Genetics)
Whole Genome Sequencing - methods
Yeast
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Summary:When the DNA polymerase that replicates the chromosome, DNA polymerase III, makes an error, there are two primary defenses against mutation: proofreading by the ϵ subunit of the holoenzyme and mismatch repair. In proofreading-deficient strains, mismatch repair is partially saturated and the cell's response to DNA damage, the SOS response, may be partially induced. To investigate the nature of replication errors, we used mutation accumulation experiments and whole-genome sequencing to determine mutation rates and mutational spectra across the entire chromosome of strains deficient in proofreading, mismatch repair, and the SOS response. We report that a proofreading-deficient strain has a mutation rate 4000-fold greater than wild-type strains. While the SOS response may be induced in these cells, it does not contribute to the mutational load. Inactivating mismatch repair in a proofreading-deficient strain increases the mutation rate another 1.5-fold. DNA polymerase has a bias for converting G:C to A:T base pairs, but proofreading reduces the impact of these mutations, helping to maintain the genomic G:C content. These findings give an unprecedented view of how polymerase and error-correction pathways work together to maintain 's low mutation rate of 1 per 1000 generations.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1534/genetics.117.300515