RecA

Function

Homologous recombination

The RecA protein binds strongly and in long clusters to ssDNA to form a nucleoprotein filament. The protein has multiple DNA binding sites, and thus can hold a single strand and double strand together. This feature makes it possible to catalyze a DNA synapsis reaction between a DNA double helix and a complementary region of single-stranded DNA. The RecA-ssDNA filament searches for sequence similarity along the dsDNA. A disordered DNA loop in RecA, Loop 2, contains the residues responsible for DNA homologous recombination. In some bacteria, RecA posttranslational modification via phosphorylation of a serine residue on Loop 2 can interfere with homologous recombination.

There are multiple proposed models for how RecA finds complementary DNA. In one model, termed conformational proofreading, the DNA duplex is stretched, which enhances sequence complementarity recognition. The reaction initiates the exchange of strands between two recombining DNA double helices. After the synapsis event, in the heteroduplex region a process called branch migration begins. In branch migration an unpaired region of one of the single strands displaces a paired region of the other single strand, moving the branch point without changing the total number of base pairs. Spontaneous branch migration can occur, however, as it generally proceeds equally in both directions it is unlikely to complete recombination efficiently. The RecA protein catalyzes unidirectional branch migration and by doing so makes it possible to complete recombination, producing a region of heteroduplex DNA that is thousands of base pairs long.

Since it is a DNA-dependent ATPase, RecA contains an additional site for binding and hydrolyzing ATP. RecA associates more tightly with DNA when it has ATP bound than when it has ADP bound.

Homologous recombination events mediated by RecA can occur in Escherichia coli during the period after DNA replication when sister loci remain close. RecA can also mediate homology pairing, homologous recombination, and DNA break repair between distant sister loci that had segregated to opposite halves of the E. coli cell.

Natural transformation

Main article: Natural competence

Natural bacterial transformation involves the transfer of DNA from one bacterium to another (ordinarily of the same species) and the integration of the donor DNA into the recipient chromosome by homologous recombination, a process mediated by the RecA protein. In some bacteria, the recA gene is induced in response to the bacterium becoming competent, the physiological state required for transformation. In Bacillus subtilis the length of the transferred DNA can be as great as a third and up to the size of the whole chromosome.

Clinical significance

RecA has been proposed as a potential drug target for bacterial infections. Small molecules that interfere with RecA function have been identified. Since many antibiotics lead to DNA damage, and all bacteria rely on RecA to fix this damage, inhibitors of RecA could be used to enhance the toxicity of antibiotics. Inhibitors of RecA may also delay or prevent the appearance of bacterial drug resistance.

References

References

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6. (December 1981). "Regulation of SOS functions: Purification of ''E. coli'' LexA protein and determination of its specific site cleaved by the RecA protein". Cell.
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10. (October 2018). "Mycobacterial Mutagenesis and Drug Resistance Are Controlled by Phosphorylation- and Cardiolipin-Mediated Inhibition of the RecA Coprotease". Molecular Cell.
11. (November 2010). "RecA-Mediated Homology Search as a Nearly Optimal Signal Detection System". Molecular Cell.
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13. (December 2021). "How strand exchange protein function benefits from ATP hydrolysis". Current Opinion in Genetics & Development.
14. (13 February 2014). "RecA bundles mediate homology pairing between distant sisters during DNA break repair". Nature.
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