Base pair substitutions caused by the uvr502 mutation affecting mutation rates and UV-sensitivity of Escherichia coli

1973 ◽  
Vol 126 (3) ◽  
pp. 255-266 ◽  
Author(s):  
G. B. Smirnov ◽  
E. V. Filkova ◽  
A. G. Skavronskaya
mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Brittany A. Niccum ◽  
Heewook Lee ◽  
Wazim MohammedIsmail ◽  
Haixu Tang ◽  
Patricia L. Foster

ABSTRACTMutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, inEscherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.IMPORTANCEIt has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. UsingEscherichia colias our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.


2019 ◽  
Author(s):  
Brittany A. Niccum ◽  
Heewook Lee ◽  
Wazim MohammedIsmail ◽  
Haixu Tang ◽  
Patricia L. Foster

AbstractMutation accumulation experiments followed by whole-genome sequencing have revealed that for several bacterial species the rate of base-pair substitutions is not constant across the chromosome but varies in a wave-like pattern symmetrical about the origin of replication. The experiments reported here demonstrate that in Escherichia coli several interacting factors determine the wave. Perturbing replication timing, progression, or the structure of the terminus disrupts the pattern. Biases in error-correction by proofreading and mismatch repair are major factors. The activities of the nucleoid binding proteins, HU and Fis, are important, suggesting that mutation rates increase when highly structured DNA is replicated. These factors should apply to most bacterial, and possibly eukaryotic, genomes, and imply that different areas of the genome evolve at different rates.


Genetics ◽  
1991 ◽  
Vol 128 (4) ◽  
pp. 695-701 ◽  
Author(s):  
J Cairns ◽  
P L Foster

Abstract Mutation rates are generally thought not to be influenced by selective forces. This doctrine rests on the results of certain classical studies of the mutations that make bacteria resistant to phages and antibiotics. We have studied a strain of Escherichia coli which constitutively expresses a lacI-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion to Lac+ is a rare event during exponential growth but occurs in stationary cultures when lactose is the only source of energy. No revertants accumulate in the absence of lactose, or in the presence of lactose if there is another, unfulfilled requirement for growth. The mechanism for such mutation in stationary phase is not known, but it requires some function of RecA which is apparently not required for mutation during exponential growth.


2003 ◽  
Vol 185 (16) ◽  
pp. 4901-4907 ◽  
Author(s):  
Pablo Castán ◽  
Lorena Casares ◽  
Jordi Barbé ◽  
José Berenguer

ABSTRACT The recA gene from Thermus thermophilus HB27 was cloned and engineered to obtain insertion (recA::kat) and deletion (ΔrecA) derivatives. Transcription of recA in this extreme thermophile was induced by mitomycin C, leading to the synthesis of a monocistronic mRNA. This DNA damage-mediated induction was dependent on the integrity of recA. In addition to UV sensitivity, the recA mutants of T. thermophilus showed severe pleiotropic defects, ranging from irregular nucleoid condensation and segregation to a dramatic reduction in viability during culture. An increase in the frequency of both carotenoidless and auxotrophic mutants within surviving cells of the ΔrecA strain indicated a high mutation rate. As RecA is not required for plasmid transformation, we have used the α-lacZ gene fragment and the ampicillin resistance gene from Escherichia coli as passenger reporters to confirm such high mutation rates. Our data support the idea that the absence of RecA results in a hypermutational phenotype in T. thermophilus. Furthermore, a direct relationship is deduced between the growth temperature and mutation rate, which finally has a deleterious effect on cell survival in the absence of RecA.


1984 ◽  
Vol 49 (0) ◽  
pp. 589-596 ◽  
Author(s):  
A.-L. Lu ◽  
K. Welsh ◽  
S. Clark ◽  
S.-S. Su ◽  
P. Modrich

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