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Updated: Jun 26, 2025

Principles of Site-Specific Recombinase SSR Technology
Published on: May 29, 2008
The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation
Michael B Cory1, Allen Li2, Christina M Hurley1
1Graduate Group in Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
The bacterial SOS response plays a key role in adaptation to DNA damage, including genomic stress caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament that forms on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete Escherichia coli SOS signal complex, constituting full-length LexA bound to RecA*. We uncover an extensive interface unexpectedly including the LexA DNA-binding domain, providing a new molecular rationale for ordered SOS gene induction. We further find that the interface involves three RecA subunits, with a single residue in the central engaged subunit acting as a molecular key, inserting into an allosteric binding pocket to induce LexA cleavage. Given the pro-mutagenic nature of SOS activation, our structural and mechanistic insights provide a foundation for developing new therapeutics to slow the evolution of antibiotic resistance.
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