RecA is a 38kilodaltonprotein essential for the repair and maintenance ofDNA inbacteria.[2] Structural and functional homologs to RecA have been found in all kingdoms of life.[3][4] RecA serves as an archetype for this class of homologousDNA repair proteins. The homologous protein is calledRAD51 ineukaryotes andRadA inarchaea.[5][6]
The RecA protein binds strongly and in long clusters to ssDNA to form a nucleoprotein filament.[9] The protein has multiple DNAbinding sites, and thus can hold a single strand and double strand together. This feature makes it possible tocatalyze a DNAsynapsis 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 DNAhomologous recombination.[10] In some bacteria, RecA posttranslational modification via phosphorylation of a serine residue on Loop 2 can interfere with homologous recombination.[11]
There are multiple proposed models for how RecA finds complementary DNA.[9] In one model, termedconformational proofreading, the DNA duplex is stretched, which enhances sequence complementarity recognition.[12][13] The reaction initiates the exchange of strands between two recombining DNA double helices. After the synapsis event, in the heteroduplex region a process calledbranch 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-dependentATPase, RecA contains an additional site for binding and hydrolyzingATP. RecAassociates more tightly with DNA when it has ATP bound than when it hasADP bound.[14]
Homologous recombination events mediated by RecA can occur inEscherichia coli during the period afterDNA replication whensister 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 theE. coli cell.[15]
Natural bacterialtransformation involves the transfer ofDNA from one bacterium to another (ordinarily of the samespecies) and the integration of the donor DNA into the recipient chromosome by homologous recombination, a process mediated by the RecA protein. In some bacteria, therecA gene is induced in response to the bacterium becomingcompetent, the physiological state required for transformation.[16] InBacillus subtilis the length of the transferred DNA can be as great as a third and up to the size of the wholechromosome.[17][18]
RecA has been proposed as a potentialdrug target for bacterial infections.[19] Small molecules that interfere with RecA function have been identified.[20][21] 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.[19]
^Brendel, Volker; Brocchieri, Luciano; Sandler, Steven J.; Clark, Alvin J.; Karlin, Samuel (May 1997). "Evolutionary Comparisons of RecA-Like Proteins Across All Major Kingdoms of Living Organisms".Journal of Molecular Evolution.44 (5):528–541.doi:10.1007/pl00006177.PMID9115177.
^Shinohara, Akira; Ogawa, Hideyuki; Ogawa, Tomoko (1992). "Rad51 protein involved in repair and recombination inS. cerevisiae is a RecA-like protein".Cell.69 (3):457–470.doi:10.1016/0092-8674(92)90447-k.PMID1581961.S2CID35937283.
^Horii, Toshihiro; Ogawa, Tomoko; Nakatani, Tomoyuki; Hase, Toshiharu; Matsubara, Hiroshi; Ogawa, Hideyuki (December 1981). "Regulation of SOS functions: Purification ofE. coli LexA protein and determination of its specific site cleaved by the RecA protein".Cell.27 (3):515–522.doi:10.1016/0092-8674(81)90393-7.PMID6101204.S2CID45482725.
^abHenkin, Tina M.; Peters, Joseph E.; Snyder, Larry; Champness, Wendy (2020).Snyder & Champness molecular genetics of bacteria (Fifth ed.). Hoboken, NJ: Wiley. pp. 368–371.ISBN9781555819750.
^Henkin, Tina M.; Peters, Joseph E.; Snyder, Larry; Champness, Wendy (2020).Snyder & Champness molecular genetics of bacteria (Fifth ed.). Hoboken, NJ: Wiley. p. 259.ISBN9781555819750.
^Saito, Yukiko; Taguchi, Hisataka; Akamatsu, Takashi (March 2006). "Fate of transforming bacterial genome following incorporation into competent cells of Bacillus subtilis: a continuous length of incorporated DNA".Journal of Bioscience and Bioengineering.101 (3):257–262.doi:10.1263/jbb.101.257.PMID16716928.
