RecA

RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is called RAD51 in eukaryotes and RadA in archaea.

SOS response
RecA has multiple activities, all related to DNA repair. In the bacterial SOS response, it has a co-protease function in the autocatalytic cleavage of the LexA repressor and the λ repressor.

Homologous recombination
RecA's association with DNA repair is based on its central role in homologous recombination. The RecA protein binds strongly and in long clusters to ssDNA to form a nucleoprotein filament. The protein has more than one DNA binding site, 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.

The search process induces stretching of the DNA duplex, which enhances sequence complementarity recognition (a mechanism termed conformational proofreading ). 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.

In Escherichia coli, homologous recombination events mediated by RecA can occur 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.

Potential as a drug target
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 serve to delay or prevent the appearance of bacterial drug resistance.

Role of RecA in natural transformation
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 B. subtilis the length of the transferred DNA can be as great as a third and up to the size of the whole chromosome.