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Motoring along with the bacterial RecA protein

Key Points

  • The bacterial RecA protein promotes the central steps in recombination and recombinational DNA repair. Homologues of RecA exist in every kingdom of living systems.

  • RecA functions as a nucleoprotein filament that encompasses the DNA. This filament facilitates the homologous alignment of two DNA molecules and the strand exchange that follows.

  • RecA is a DNA-dependent ATPase. The basic DNA-pairing and strand-exchange functions of RecA do not require ATP hydrolysis. However, bacterial RecA couples several additional reactions to ATP hydrolysis, reactions that are not promoted by its archaeal and eukaryotic homologues.

  • The unique activities of RecA include the bypass of heterologous insertions in the duplex DNA substrate of strand exchange, four-strand exchange, replication-fork regression and an indirect helicase activity. These reactions feature the movement of DNA branches over thousands of base pairs and/or the complete unwinding of segments of duplex DNA. RecA is therefore a motor protein.

  • A model for the coupling of ATP hydrolysis to DNA-strand exchange that involves the rotation of two DNA molecules about each other is most consistent with the unusual reactions that are promoted by RecA.

  • At a stalled replication fork, RecA has the capacity to either unwind the DNA ahead of the fork or to regress the fork, depending on the disposition of the assembled RecA filament.

Abstract

The recombinases of the RecA family are often viewed only as DNA-pairing proteins — they bind to one DNA segment, align it with homologous sequences in another DNA segment, promote an exchange of DNA strands and then dissociate. To a first approximation, this description seems to fit the eukaryotic (Rad51 and Dmc1) and archaeal (RadA) RecA homologues. However, the bacterial RecA protein does much more, coupling ATP hydrolysis with DNA-strand exchange in a manner that greatly expands its repertoire of activities. This article explores the protein activities and experimental results that have identified RecA as a motor protein.

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Figure 1: Activities of Escherichia coli RecA.
Figure 2: Assembly of RecA filaments.
Figure 3: RecA reactions that depend on ATP hydrolysis.
Figure 4: Models for RecA-mediated DNA-strand exchange coupled to ATP hydrolysis.
Figure 5: An intermittent DNA-pairing structure as an intermediate in DNA-strand exchange.

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Acknowledgements

Work cited from the author's laboratory was supported by the National Institutes of Health.

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Supplementary information S1 (movie)

Coupling ATP hydrolysis to DNA-strand exchange. In a RecA filament that promotes DNA-strand exchange, ATP hydrolysis is organized in waves that are six subunits apart. The subunits in a particular stage of the ATP hydrolytic cycle are therefore aligned longitudinally along the filament, as shown. The waves move through the filament at almost exactly the rate depicted under standard reaction conditions at37°C.Reproduced with permission from Ref. 1. (MOV 148 kb)

References

1. Cox, J. M., Tsodikov, O. V. & Cox, M. M. Organized unidirectional waves of ATP hydrolysis within a RecA filament PLos. Biol. 3, 231–243 (2005).

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Glossary

Recombinational DNA repair

A DNA-repair process that involves the strand-displacement and strand-exchange reactions of homologous recombination mechanisms.

Conjugation

A process by which plasmid or chromosomal DNA is actively transferred from one bacterium to another. Recombination that follows the DNA transfer provides the basis for genetic exchanges.

Collapsed replication fork

A replication fork that has encountered a DNA lesion, often a break in a template strand, that results in the disassembly of replication enzymes.

Fork regression

A reaction in which a replication fork is reversed so as to repair the template strands and displace the newly synthesized strands.

Translesion DNA polymerase

A class of DNA polymerases that exhibit a reduced fidelity in DNA synthesis that allows them to replicate through a DNA lesion in the template strand. Translesion DNA synthesis often results in a higher than normal level of introduced mutations.

SOS regulon

A set of coordinately regulated genes that are all repressed by the LexA protein and that encode an organized cellular response to heavy DNA damage.

Indirect helicase

DNA-strand separation brought about by the activity of RecA functioning on DNA segments that are adjacent to the region being unwound.

Lagging strand

The template strand that directs DNA synthesis in the direction that is opposite to that in which the fork is proceeding.

Leading strand

The template strand that directs DNA synthesis in the same direction as the fork is proceeding.

Holliday junction

A DNA structure, often a recombination intermediate, in which two duplex DNAs are linked by a two-strand DNA crossover.

Heteroduplex DNA

A duplex in which each strand is derived from different DNA molecules.

ssDNA-binding protein

(SSB). A class of protein, found in all cells, that binds to single-stranded (ss)DNA and interacts with many other proteins that are involved in DNA metabolism.

Topoisomerase

An enzyme that changes DNA topology by increasing or decreasing the twist of the DNA.

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Cox, M. Motoring along with the bacterial RecA protein. Nat Rev Mol Cell Biol 8, 127–138 (2007). https://doi.org/10.1038/nrm2099

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