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Bacterial phenotypic heterogeneity in DNA repair and mutagenesis

Abstract:
Genetically identical cells frequently exhibit striking heterogeneity in various phenotypic traits such as their morphology, growth rate, or gene expression. Such non-genetic diversity can help clonal bacterial populations overcome transient environmental challenges without compromising genome stability, while genetic change is required for long-term heritable adaptation. At the heart of the balance between genome stability and plasticity are the DNA repair pathways that shield DNA from lesions and reverse errors arising from the imperfect DNA replication machinery. In principle, phenotypic heterogeneity in the expression and activity of DNA repair pathways can modulate mutation rates in single cells and thus be a source of heritable genetic diversity, effectively reversing the genotype-to-phenotype dogma. Long-standing evidence for mutation rate heterogeneity comes from genetics experiments on cell populations, which are now complemented by direct measurements on individual living cells. These measurements are increasingly performed using fluorescence microscopy with a temporal and spatial resolution that enables localising, tracking, and counting proteins with single-molecule sensitivity. In this review, we discuss which molecular processes lead to phenotypic heterogeneity in DNA repair and consider the potential consequences on genome stability and dynamics in bacteria. We further inspect these concepts in the context of DNA damage and mutation induced by antibiotics.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1042/bst20190364

Authors


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Role:
Author
ORCID:
0000-0001-8431-7504
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Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
ORCID:
0000-0002-3579-0888



Publisher:
Portland Press
Journal:
Biochemical Society Transactions More from this journal
Volume:
48
Issue:
2
Pages:
451-462
Publication date:
2020-03-20
Acceptance date:
2020-02-28
DOI:
EISSN:
1470-8752
ISSN:
0300-5127
Pmid:
32196548


Language:
English
Keywords:
Pubs id:
1097404
Local pid:
pubs:1097404
Deposit date:
2020-06-08

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