A mechanism for induction of the SOS response in E. coli: insights into the regulation of reversible protein polymerization in vivo.
During normal DNA replication, RecA, the principal recombinational repair enzyme of E. coli, cannot assemble its filament on SSB-bound single-stranded DNA at the replication forks. This behavior is paralleled in vitro, where at low Mg2+ concentrations RecA can not polymerize on SSB-bound single-stranded DNA. Inhibition of DNA replication in vivo renders 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, abundant in vitro observations 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 synthesis in vivo leads 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.
Kuzminov
A
A
Institute of Molecular Biology, University of Oregon, Eugene 97403, USA.
D000199:Actins / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis; D004277:DNA, Single-Stranded / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008957:Models, Genetic; D011108:Polymers; D011938:Rec A Recombinases / Q000096:biosynthesis*; D013014:SOS Response, Genetics; D013095:Spermidine / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D011108:Polymers; D014404:Tubulin; D011938:Rec A Recombinases; D008274:Magnesium; D013095:Spermidine