Oxidative DNA damage is instrumental in hyperreplication stress-induced inviability of Escherichia coli
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Oxidative DNA damage is instrumental in hyperreplication stress-induced inviability of Escherichia coli. / Charbon, Godefroid; Bjørn, Louise; Mendoza-Chamizo, Belén; Frimodt-Møller, Jakob; Løbner-Olesen, Anders.
I: Nucleic Acids Research, Bind 42, Nr. 21, 2014, s. 13228-13241.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Oxidative DNA damage is instrumental in hyperreplication stress-induced inviability of Escherichia coli
AU - Charbon, Godefroid
AU - Bjørn, Louise
AU - Mendoza-Chamizo, Belén
AU - Frimodt-Møller, Jakob
AU - Løbner-Olesen, Anders
N1 - © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2014
Y1 - 2014
N2 - In Escherichia coli, an increase in the ATP bound form of the DnaA initiator protein results in hyperinitiation and inviability. Here, we show that such replication stress is tolerated during anaerobic growth. In hyperinitiating cells, a shift from anaerobic to aerobic growth resulted in appearance of fragmented chromosomes and a decrease in terminus concentration, leading to a dramatic increase in ori/ter ratio and cessation of cell growth. Aerobic viability was restored by reducing the level of reactive oxygen species (ROS) or by deleting mutM (Fpg glycosylase). The double-strand breaks observed in hyperinitiating cells therefore results from replication forks encountering single-stranded DNA lesions generated while removing oxidized bases, primarily 8-oxoG, from the DNA. We conclude that there is a delicate balance between chromosome replication and ROS inflicted DNA damage so the number of replication forks can only increase when ROS formation is reduced or when the pertinent repair is compromised.
AB - In Escherichia coli, an increase in the ATP bound form of the DnaA initiator protein results in hyperinitiation and inviability. Here, we show that such replication stress is tolerated during anaerobic growth. In hyperinitiating cells, a shift from anaerobic to aerobic growth resulted in appearance of fragmented chromosomes and a decrease in terminus concentration, leading to a dramatic increase in ori/ter ratio and cessation of cell growth. Aerobic viability was restored by reducing the level of reactive oxygen species (ROS) or by deleting mutM (Fpg glycosylase). The double-strand breaks observed in hyperinitiating cells therefore results from replication forks encountering single-stranded DNA lesions generated while removing oxidized bases, primarily 8-oxoG, from the DNA. We conclude that there is a delicate balance between chromosome replication and ROS inflicted DNA damage so the number of replication forks can only increase when ROS formation is reduced or when the pertinent repair is compromised.
KW - Adenosine Triphosphatases
KW - Aerobiosis
KW - Anaerobiosis
KW - Chromosomes, Bacterial
KW - DNA Breaks, Double-Stranded
KW - DNA Damage
KW - DNA Repair
KW - DNA Replication
KW - DNA, Bacterial
KW - Escherichia coli
KW - Escherichia coli Proteins
KW - Microbial Viability
KW - Mutation
KW - Oxidative Stress
U2 - 10.1093/nar/gku1149
DO - 10.1093/nar/gku1149
M3 - Journal article
C2 - 25389264
VL - 42
SP - 13228
EP - 13241
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 21
ER -
ID: 131364647