During normal DNA replication, RecA, the principal recombinational repair enzyme ofE. coli, cannot assemble its filament on SSB-bound single-stranded DNA at the replication forks. This behavior is paralleledin vitro, where at low Mg2+concentrations RecA can not polymerize on SSB-bound single-stranded DNA. Inhibition of DNA replicationin vivorenders RecA able to polymerize on SSB-bound single-stranded DNA and to activate the SOS response. Although the mechanism of SOS induction is still obscure, abundantin vitroobservations indicate that RecA filament formation on SSB-bound single-stranded DNA is facilitated at elevated concentrations of ATP, Mg2+and spermidine. It is proposed here that inhibition of DNA synthesisin vivoleads to a similar accumulation of ATP and its counter-ions, Mg2+and spermidine, resulting ultimately in SOS induction. When DNA synthesis is restored, the concentration of ATP, Mg2+and spermidine returns to normal levels, favoring RecA depolymerization. On the basis of the known structure of RecA, a mechanism for reversible RecA polymerization is presented. In a RecA polymer, the monomers are known to interact with each other primarily through hydrophobic, oppositely charged surfaces. In conditions suboptimal for polymerization, these hydrophobic surfaces of the monomers are possibly masked by electrostatic interactions with other, oppositely charged domains of the monomers. There are known recombinational repair proteins whose specific functions are likely to assist in RecA polymerization or depolymerization. Features of reversible polymerization of eukaryotic proteins tubulin and actin are consistent with the possibility that RecA exploits a general principle for the regulation of reversible protein polymerization.
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Agricultural and Biological Sciences(all)
- Applied Mathematics