scholarly journals Nucleotide Excision Repair Is a Predominant Mechanism for Processing Nitrofurazone-Induced DNA Damage in Escherichia coli

2009 ◽  
Vol 191 (15) ◽  
pp. 4959-4965 ◽  
Author(s):  
Katherine R. Ona ◽  
Charmain T. Courcelle ◽  
Justin Courcelle
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Short Exposure ◽  
Direct Inhibition ◽  
Pol Iv ◽  
Primary Mechanism ◽  
Nucleotide Excision ◽  
High Concentrations

ABSTRACT Nitrofurazone is reduced by cellular nitroreductases to form N 2-deoxyguanine (N 2-dG) adducts that are associated with mutagenesis and lethality. Much attention recently has been given to the role that the highly conserved polymerase IV (Pol IV) family of polymerases plays in tolerating adducts induced by nitrofurazone and other N 2-dG-generating agents, yet little is known about how nitrofurazone-induced DNA damage is processed by the cell. In this study, we characterized the genetic repair pathways that contribute to survival and mutagenesis in Escherichia coli cultures grown in the presence of nitrofurazone. We find that nucleotide excision repair is a primary mechanism for processing damage induced by nitrofurazone. The contribution of translesion synthesis to survival was minor compared to that of nucleotide excision repair and depended upon Pol IV. In addition, survival also depended on both the RecF and RecBCD pathways. We also found that nitrofurazone acts as a direct inhibitor of DNA replication at higher concentrations. We show that the direct inhibition of replication by nitrofurazone occurs independently of DNA damage and is reversible once the nitrofurazone is removed. Previous studies that reported nucleotide excision repair mutants that were fully resistant to nitrofurazone used high concentrations of the drug (200 μM) and short exposure times. We demonstrate here that these conditions inhibit replication but are insufficient in duration to induce significant levels of DNA damage.

The role of nucleotide excision repair of Escherichia coli in repair of spontaneous and gamma-radiation-induced DNA damage in the lacZα gene

2000 ◽  
Vol 460 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Gitta K Kuipers ◽  
Ben J Slotman ◽  
Hester A Poldervaart ◽  
Ingrid M.J van Vilsteren ◽  
Carola A Reitsma-Wijker ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Gamma Radiation ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nucleotide Excision ◽  
Radiation Induced

scholarly journals The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

1999 ◽  
Vol 27 (16) ◽  
pp. 3276-3282 ◽  
Author(s):  
P. P. H. Van Sloun ◽  
J. G. Jansen ◽  
G. Weeda ◽  
L. H. F. Mullenders ◽  
A. A. van Zeeland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Embryonic Stem ◽  
Genotoxic Effects ◽  
Nucleotide Excision

scholarly journals Flipping of alkylated DNA damage bridges base and nucleotide excision repair

Nature ◽  
2009 ◽  
Vol 459 (7248) ◽  
pp. 808-813 ◽  
Author(s):  
Julie L. Tubbs ◽  
Vitaly Latypov ◽  
Sreenivas Kanugula ◽  
Amna Butt ◽  
Manana Melikishvili ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nucleotide Excision

scholarly journals Photolyases from Saccharomyces cerevisiae and Escherichia coli recognize common binding determinants in DNA containing pyrimidine dimers.

1989 ◽  
Vol 9 (11) ◽  
pp. 4777-4788 ◽  
Author(s):  
M Baer ◽  
G B Sancar
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Spectroscopic Studies ◽  
Pyrimidine Dimer ◽  
Nucleotide Sequence Analysis ◽  
Binding Motif ◽  
Pyrimidine Dimers ◽  
Nucleotide Excision

DNA photolyases catalyze the light-dependent repair of pyrimidine dimers in DNA. The results of nucleotide sequence analysis and spectroscopic studies demonstrated that photolyases from Saccharomyces cerevisiae and Escherichia coli share 37% amino acid sequence homology and contain identical chromophores. Do the similarities between these two enzymes extend to their interactions with DNA containing pyrimidine dimers, or does the organization of DNA into nucleosomes in S. cerevisiae necessitate alternative or additional recognition determinants? To answer this question, we used chemical and enzymatic techniques to identify the contacts made on DNA by S. cerevisiae photolyase when it is bound to a pyrimidine dimer and compared these contacts with those made by E. coli photolyase and by a truncated derivative of the yeast enzyme when bound to the same substrate. We found evidence for a common set of interactions between the photolyases and specific phosphates in the backbones of both strands as well as for interactions with bases in both the major and minor grooves of dimer-containing DNA. Superimposed on this common pattern were significant differences in the contributions of specific contacts to the overall binding energy, in the interactions of the enzymes with groups on the complementary strand, and in the extent to which other DNA-binding proteins were excluded from the region around the dimer. These results provide strong evidence both for a conserved dimer-binding motif and for the evolution of new interactions that permit photolyases to also act as accessory proteins in nucleotide excision repair. The locations of the specific contacts made by the yeast enzyme indicate that the mechanism of nucleotide excision repair in this organism involves incision(s) at a distance from the pyrimidine dimer.

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