1. Bacterial phenotypic heterogeneity in DNA repair and mutagenesis
- Author
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Maxence S Vincent and Stephan Uphoff
- Subjects
DNA Replication ,DNA, Bacterial ,Mutation rate ,antibiotic resistance ,DNA Repair ,Genotype ,DNA repair ,DNA damage ,Biology ,Bacterial Physiological Phenomena ,medicine.disease_cause ,Microbiology ,Biochemistry ,Genomic Instability ,DNA synthesis and repair ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,single-cell analysis ,DNA, Chromosomes & Chromosomal Structure ,Review Articles ,030304 developmental biology ,Genetics ,0303 health sciences ,Mutation ,Bacteria ,Gene Expression & Regulation ,Genetic heterogeneity ,Mutagenesis ,DNA replication ,Genetic Variation ,Anti-Bacterial Agents ,phenotypic heterogeneity ,Phenotype ,chemistry ,DNA replication and recombination ,Genome, Bacterial ,030217 neurology & neurosurgery ,DNA ,DNA Damage - 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.
- Published
- 2020