PMID:21912525

Citation	Adikesavan, AK, Katsonis, P, Marciano, DC, Lua, R, Herman, C and Lichtarge, O (2011) Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites. PLoS Genet. 7:e1002244
Abstract	RecA plays a key role in homologous recombination, the induction of the DNA damage response through LexA cleavage and the activity of error-prone polymerase in Escherichia coli. RecA interacts with multiple partners to achieve this pleiotropic role, but the structural location and sequence determinants involved in these multiple interactions remain mostly unknown. Here, in a first application to prokaryotes, Evolutionary Trace (ET) analysis identifies clusters of evolutionarily important surface amino acids involved in RecA functions. Some of these clusters match the known ATP binding, DNA binding, and RecA-RecA homo-dimerization sites, but others are novel. Mutation analysis at these sites disrupted either recombination or LexA cleavage. This highlights distinct functional sites specific for recombination and DNA damage response induction. Finally, our analysis reveals a composite site for LexA binding and cleavage, which is formed only on the active RecA filament. These new sites can provide new drug targets to modulate one or more RecA functions, with the potential to address the problem of evolution of antibiotic resistance at its root.
Links	PubMed PMC3164682 Online version:10.1371/journal.pgen.1002244
Keywords	Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Evolution, Molecular; Homologous Recombination/genetics; Mutagenesis, Site-Directed; Protein Conformation; Protein Interaction Domains and Motifs/genetics; Rec A Recombinases/genetics; Rec A Recombinases/metabolism; SOS Response (Genetics)/genetics; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECOLI:RECA	involved_in	GO:0006310: DNA recombination	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
ECOLI:RECA		GO:0006310: DNA recombination	ECO:0000315:		P		Figure 5B showed all three mutant strains had reduced recombination efficiency of RecA	complete CACAO 3951
ECOLI:LEXA	Contributes to	GO:0009432: SOS response	ECO:0000314:		P		Figure 3:RecA extended interface patch residues are involved in RecA active filament formation. The bacterial recombinase protein RecA is pivotal to DNA repair [1]–[4] and to orchestrate the bacterial DNA damage response (SOS response) against natural, or drug-induced, genotoxic conditions.	complete
ECOLI:LEXA	Contributes to	GO:0009432:	ECO:0000315:				Figure 3:RecA extended interface patch residues are involved in RecA active filament formation. The bacterial recombinase protein RecA is pivotal to DNA repair [1]–[4] and to orchestrate the bacterial DNA damage response (SOS response) against natural, or drug-induced, genotoxic conditions.	complete

References

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