Nonhomologous End-Joining in Bacteria: A Microbial Perspective

Pitcher, R. S.; Brissett, Nigel C.; Doherty, Aidan J.

doi:10.1146/annurev.micro.61.080706.093354

Cited by 142 publications

(161 citation statements)

References 96 publications

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“…Mutations in the DNA Pol III or the mismatch repair system increase the rates of illegitimate recombination (347,348). Some bacteria (e.g., B. subtilis, Mycobacterium tuberculosis, Mycobacterium smegmatis, and P. aeruginosa) encode a bona fide nonhomologous end-joining (NHEJ) system (349)(350)(351)(352)(353). This system consists of the Ku and LigD proteins, which act together to rejoin DNA ends at DNA sequences containing microhomologies.…”

Section: Mechanisms Of Homologous and Illegitimate Recombinationmentioning

confidence: 99%

Bacterial Genome Instability

Darmon

Leach

2014

Microbiol Mol Biol Rev

345

289

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SUMMARY Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease.

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Section: Mechanisms Of Homologous and Illegitimate Recombinationmentioning

confidence: 99%

Bacterial Genome Instability

Darmon

Leach

2014

Microbiol Mol Biol Rev

345

289

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“…Thus, the activity of the NHEJ pathway is dependent upon ATP generation during spore germination. In the NHEJ systems of bacterial species such as Mycobacterium smegmatis and Pseudomonas aeruginosa, the ATP-dependent DNA ligase is a multidomain protein composed of polymerase and nuclease domains in addition to the core ligase domain (49). However, in the Bacillus subtilis NHEJ ligase YkoU, the nuclease domain appears to be absent and the polymerase domain is fused with core ligase domain (reviewed in reference 49).…”

Section: Vol 190 2008 Notes 1135mentioning

confidence: 99%

Roles of the Major, Small, Acid-Soluble Spore Proteins and Spore-Specific and Universal DNA Repair Mechanisms in Resistance of Bacillus subtilis Spores to Ionizing Radiation from X Rays and High-Energy Charged-Particle Bombardment

et al. 2008

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The role of DNA repair by nonhomologous end joining (NHEJ), homologous recombination, spore photoproduct lyase, and DNA polymerase I and genome protection via ␣/␤-type small, acid-soluble spore proteins (SASP) in Bacillus subtilis spore resistance to accelerated heavy ions (high-energy charged [HZE] particles) and X rays has been studied. Spores deficient in NHEJ and ␣/␤-type SASP were significantly more sensitive to HZE particle bombardment and X-ray irradiation than were the recA, polA, and splB mutant and wild-type spores, indicating that NHEJ provides an efficient DNA double-strand break repair pathway during spore germination and that the loss of the ␣/␤-type SASP leads to a significant radiosensitivity to ionizing radiation, suggesting the essential function of these spore proteins as protectants of spore DNA against ionizing radiation.Endospores of the gram-positive bacterium Bacillus subtilis are highly resistant to inactivation by environmental stresses, such as biocidal agents and toxic chemicals, desiccation, pressure and temperature extremes, and high fluences of UV radiation (reviewed in references 44, 45, and 61) and are a powerful biodosimetric system for terrestrial environmental monitoring and astrobiological studies (44). On Earth, understanding extreme spore resistance to ionizing radiation is important in the areas of food preservation, medical sterilization, and decontamination from bioterror attack (4, 17, 47; reviewed in references 42 and 43). Off Earth, spore radiation resistance is important both in space flight and in ground-based simulations, in order to obtain information on the biological damage produced by exposure to space conditions (23,25,26,44). Onboard several spacecraft (Apollo 16, Spacelab 1, LDEF, D2, and FOTON), spores of Bacillus subtilis were exposed to selected parameters of space, such as space vacuum and different spectral ranges of solar UV radiation and cosmic rays, applied separately or in combination (5, 9, 19-21, 23, 24, 26). Especially, the radiation environment on Earth, on Mars, in low-Earth orbit, and in deep space is typified by a wide variety of primary particles covering an extended range of energies. Galactic cosmic rays (GCR) are charged particles that originate from sources beyond our solar system. The distribution of GCR is believed to be isotropic throughout interstellar space. The spectrum of the GCR consists of 98% protons and heavier ions (baryon component) and 2% electrons and positrons (lepton component). The baryon component is composed of 87% protons, 12% helium ions (alpha particles), and the remaining 1% heavy ions of charge 3 from lithium to 92 from uranium. Due to their high abundance, iron ions are highly penetrating, giving them a large potential for radiobiological damage (3,21).While the UV photochemistry of spore DNA and repair of UV damage to DNA during germination are well characterized (34,44,(59)(60)(61), there has been relatively little work on the nature of DNA damage in spores caused by ionizing radiation, the protective role of...

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“…In B. subtilis, a number of proteins have been shown to function in promoting homologous recombination either by assaying for DNA uptake and integration or through the study of DNA damaging agents, called clastogens, that require homologous recombination for repair (for a review, see references 3 and 4). These approaches have helped define the RecA-dependent homologous recombination and the RecA-independent nonhomologous end-joining (NHEJ) pathways in B. subtilis (3,(5)(6)(7).…”

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confidence: 99%

MutS2 Promotes Homologous Recombination in Bacillus subtilis

Burby

Simmons

2017

J Bacteriol

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Bacterial MutS proteins are subdivided into two families, MutS1 and MutS2. MutS1 family members recognize DNA replication errors during their participation in the well-characterized mismatch repair (MMR) pathway. In contrast to the well-described function of MutS1, the function of MutS2 in bacteria has remained less clear. In Helicobacter pylori and Thermus thermophilus, MutS2 has been shown to suppress homologous recombination. The role of MutS2 is unknown in the Grampositive bacterium Bacillus subtilis. In this work, we investigated the contribution of MutS2 to maintaining genome integrity in B. subtilis. We found that deletion of mutS2 renders B. subtilis sensitive to the natural antibiotic mitomycin C (MMC), which requires homologous recombination for repair. We demonstrate that the C-terminal small MutS-related (Smr) domain is necessary but not sufficient for tolerance to MMC. Further, we developed a CRISPR/Cas9 genome editing system to test if the inducible prophage PBSX was the underlying cause of the observed MMC sensitivity. Genetic analysis revealed that MMC sensitivity was dependent on recombination and not on nucleotide excision repair or a symptom of prophage PBSX replication and cell lysis. We found that deletion of mutS2 resulted in decreased transformation efficiency using both plasmid and chromosomal DNA. Further, deletion of mutS2 in a strain lacking the Holliday junction endonuclease gene recU resulted in increased MMC sensitivity and decreased transformation efficiency, suggesting that MutS2 could function redundantly with RecU. Together, our results support a model where B. subtilis MutS2 helps to promote homologous recombination, demonstrating a new function for bacterial MutS2.IMPORTANCE Cells contain pathways that promote or inhibit recombination. MutS2 homologs are Smr-endonuclease domain-containing proteins that have been shown to function in antirecombination in some bacteria. We present evidence that B. subtilis MutS2 promotes recombination, providing a new function for MutS2. We found that cells lacking mutS2 are sensitive to DNA damage that requires homologous recombination for repair and have reduced transformation efficiency. Further analysis indicates that the C-terminal Smr domain requires the N-terminal portion of MutS2 for function in vivo. Moreover, we show that a mutS2 deletion is additive with a recU deletion, suggesting that these proteins have a redundant function in homologous recombination. Together, our study shows that MutS2 proteins have adapted different functions that impact recombination.

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Nonhomologous End-Joining in Bacteria: A Microbial Perspective

Cited by 142 publications

References 96 publications

Bacterial Genome Instability

Bacterial Genome Instability

Roles of the Major, Small, Acid-Soluble Spore Proteins and Spore-Specific and Universal DNA Repair Mechanisms in Resistance of Bacillus subtilis Spores to Ionizing Radiation from X Rays and High-Energy Charged-Particle Bombardment

MutS2 Promotes Homologous Recombination in Bacillus subtilis

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