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  • Review Article
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Bacterial DNA excision repair pathways

Abstract

Bacteria are continuously exposed to numerous endogenous and exogenous DNA-damaging agents. To maintain genome integrity and ensure cell survival, bacteria have evolved several DNA repair pathways to correct different types of DNA damage and non-canonical bases, including strand breaks, nucleotide modifications, cross-links, mismatches and ribonucleotide incorporations. Recent advances in genome-wide screens, the availability of thousands of whole-genome sequences and advances in structural biology have enabled the rapid discovery and characterization of novel bacterial DNA repair pathways and new enzymatic activities. In this Review, we discuss recent advances in our understanding of base excision repair and nucleotide excision repair, and we discuss several new repair processes including the EndoMS mismatch correction pathway and the MrfAB excision repair system.

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Fig. 1: Examples of endogenous and exogenous sources of DNA damage encountered by bacteria.
Fig. 2: Advances in base excision repair.
Fig. 3: Azinomycin B and nitrogen mustard inter-strand cross-link repair.
Fig. 4: Overview of nucleotide excision repair.
Fig. 5: Structural insights into EndoMS restriction endonuclease activity.
Fig. 6: Role of MrfA in DNA repair.

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Acknowledgements

The authors thank the referees for their helpful comments on this work. They also acknowledge that owing to space limitation many important studies and citations could not be included. Work in the authors’ laboratory was funded by the National Institutes of Health (NIH) grant GM131772 to L.A.S. K.J.W. was supported by funding from the NIH Cellular Biotechnology Training Grant (T32 GM008353) and a predoctoral fellowship from the National Science Foundation (NSF) (#DEG 1256260).

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Correspondence to Lyle A. Simmons.

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Nature Reviews Microbiology thanks Stewart Shuman; Umesh Varshney, who co-reviewed with Indu Kapoor; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Replication fork

Where the replicative machinery binds and synthesizes the leading and lagging DNA strands.

Photoreactivation

Direct reversal of pyrimidine dimers using photolyase.

Base excision repair

(BER). Repair of base damage and non-canonical bases using a DNA glycosylase.

Nucleotide excision repair

(NER). Repair of bulky, helix-distorting lesions within DNA following excision of an approximately 10–12-nucleotide patch.

Homologous recombination

Repair of a DNA break using homologous DNA.

Non-homologous end joining

The process by which two ends of DNA (from a double-stranded DNA break) with little to no homology are processed and joined together to repair the break.

Photoproducts

Bulky lesions resulting from UV damage.

δ-Elimination

Removal of the sugar moiety remaining after an apurinic/apyrimidinic (AP) site is created leaving behind phosphates on the 3′ and 5′ ends.

CH–π interactions

Non-covalent stacking interaction between the carbon–hydrogen bond of a nucleobase and an aromatic residue of a non-flipping DNA glycosylase that aids in cleavage of a glycosidic bond.

Nitrogen mustards

Non-specific DNA alkylating organic compounds.

Type II restriction systems

Enzymes that specifically recognize a site within DNA for methylation and cleavage.

π–π stacking

Non-covalent interactions between aromatic rings of a protein.

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Wozniak, K.J., Simmons, L.A. Bacterial DNA excision repair pathways. Nat Rev Microbiol 20, 465–477 (2022). https://doi.org/10.1038/s41579-022-00694-0

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