Bacterial autoimmunity due to a restriction-modification system

Maroš Pleška, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto, Edo Kussell, Cəlin C. Guet

Research output: Contribution to journalArticle

Abstract

Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes.

Original languageEnglish (US)
Pages (from-to)404-409
Number of pages6
JournalCurrent Biology
Volume26
Issue number3
DOIs
StatePublished - Feb 8 2016

Fingerprint

DNA Restriction-Modification Enzymes
autoimmunity
restriction endonucleases
Autoimmunity
DNA
DNA Cleavage
Genome
Genes
genome
Stochastic Processes
SOS response (genetics)
Double-Stranded DNA Breaks
DNA Restriction Enzymes
Methyltransferases
stochastic processes
DNA Repair
Bacteriophages
methyltransferases
Genetic Recombination
prokaryotic cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pleška, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E., & Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification system. Current Biology, 26(3), 404-409. https://doi.org/10.1016/j.cub.2015.12.041

Bacterial autoimmunity due to a restriction-modification system. / Pleška, Maroš; Qian, Long; Okura, Reiko; Bergmiller, Tobias; Wakamoto, Yuichi; Kussell, Edo; Guet, Cəlin C.

In: Current Biology, Vol. 26, No. 3, 08.02.2016, p. 404-409.

Research output: Contribution to journalArticle

Pleška, M, Qian, L, Okura, R, Bergmiller, T, Wakamoto, Y, Kussell, E & Guet, CC 2016, 'Bacterial autoimmunity due to a restriction-modification system', Current Biology, vol. 26, no. 3, pp. 404-409. https://doi.org/10.1016/j.cub.2015.12.041
Pleška M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E et al. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 2016 Feb 8;26(3):404-409. https://doi.org/10.1016/j.cub.2015.12.041
Pleška, Maroš ; Qian, Long ; Okura, Reiko ; Bergmiller, Tobias ; Wakamoto, Yuichi ; Kussell, Edo ; Guet, Cəlin C. / Bacterial autoimmunity due to a restriction-modification system. In: Current Biology. 2016 ; Vol. 26, No. 3. pp. 404-409.
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