title: RecA: Regulation and Mechanism of a Molecular Search Engine.
abstract: Homologous recombination maintains genomic integrity by repairing broken chromosomes. The broken chromosome is partially resected to produce single-stranded DNA (ssDNA) that is used to search for homologous double-stranded DNA (dsDNA). This homology driven 'search and rescue' is catalyzed by a class of DNA strand exchange proteins that are defined in relation to Escherichia coli RecA, which forms a filament on ssDNA. Here, we review the regulation of RecA filament assembly and the mechanism by which RecA quickly and efficiently searches for and identifies a unique homologous sequence among a vast excess of heterologous DNA. Given that RecA is the prototypic DNA strand exchange protein, its behavior affords insight into the actions of eukaryotic RAD51 orthologs and their regulators, BRCA2 and other tumor suppressors.
authors.affiliation: Department of Microbiology and Molecular Genetics and Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Bell
authors.affiliation: Department of Microbiology and Molecular Genetics and Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA. Electronic address: sckowalczykowski@ucdavis.edu.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Kowalczykowski
mesh_terms: D024682:BRCA2 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D059765:Homologous Recombination; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011938:Rec A Recombinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D059767:Recombinational DNA Repair; D017386:Sequence Homology, Amino Acid
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D011938:Rec A Recombinases
keywords: Förster resonance energy transfer (FRET); RAD51; homology search; recombination; self-assembly; single molecule imaging; total internal reflection fluorescence (TIRF)