title: Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Anbu K
authors.initials: AK
authors.lastname: Adikesavan
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Katsonis
authors.forename: David C
authors.initials: DC
authors.lastname: Marciano
authors.forename: Rhonald
authors.initials: R
authors.lastname: Lua
authors.forename: Christophe
authors.initials: C
authors.lastname: Herman
authors.forename: Olivier
authors.initials: O
authors.lastname: Lichtarge
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D059765:Homologous Recombination / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism*; D013014:SOS Response, Genetics / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D011938:Rec A Recombinases; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein