Abstract
The linear chromosome of the bacterium Streptomyces exhibits a remarkable genetic organization with grossly a central conserved region flanked by variable chromosomal arms. The terminal diversity co-locates with an intense DNA plasticity including the occurrence of large deletions associated to circularization and chromosomal arm exchange. These observations prompted us to assess the role of double strand break (DSB) repair in chromosome plasticity following. For that purpose, DSBs were induced along the chromosome using the meganuclease I-SceI. DSB repair in the central region of the chromosome was mutagenic at the healing site but kept intact the whole genome structure. In contrast, DSB repair in the chromosomal arms was mostly associated to the loss of the targeted chromosomal arm and extensive deletions beyond the cleavage sites. While homologous recombination occurring between copies of DNA sequences accounted for the most part of the chromosome rescue events, Non Homologous End Joining was involved in mutagenic repair as well as in huge genome rearrangements (i.e. circularization). Further, NHEJ repair was concomitant with the integration of genetic material at the healing site. We postulate that DSB repair drives genome plasticity and evolution in Streptomyces and that NHEJ may foster horizontal transfer in the environment.
Highlights
The soil bacterium Streptomyces is renowned for its biotechnological capabilities, most notably its ability to synthesize a wide variety of bioactive secondary metabolites used in medicine as antiproliferative agents[1]
The Non Homologous End Joining (NHEJ) pathway was long considered as the hallmark of eukaryotes, suggesting that Double-Strand Break (DSB) repair in prokaryotes fully relies on homologous recombination (HR)
To monitor the consequences of DSB repair along the Streptomyces chromosome, we developed a DSB inducible system based on the meganuclease I-SceI heterologous expression
Summary
The soil bacterium Streptomyces is renowned for its biotechnological capabilities, most notably its ability to synthesize a wide variety of bioactive secondary metabolites used in medicine as antiproliferative agents (antibiotics, anticancer and antifungal drugs)[1] This group of bacteria possesses unique genome characteristics among which a high GC content (circa 72%) and a large linear chromosome (6–12 Mb) ended by inverted repeats. During culture, Streptomyces species offsprings present between 0.1 and 1% of spontaneous mutants defective in morphological and physiological differentiation including secondary metabolic pathways[5]. This phenotypic instability correlates with the formation of large deletions affecting the chromosomal arms. The involvement of all NHEJ-like genes, including the ‘variable’ set, in DNA damage response in Streptomyces suggests that in these organisms, a more complex pathway than in Mycobacterium or Bacillus is present
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