title: Preferential DNA damage prevention by the E. coli AidB gene: A new mechanism for the protection of specific genes.
abstract: aidB is one of the four genes of E. coli that is induced by alkylating agents and regulated by Ada protein. Three genes (ada, alkA, and alkB) encode DNA repair proteins that remove or repair alkylated bases. However, the role of AidB remains unclear despite extensive efforts to determine its function in cells exposed to alkylating agents. The E. coli AidB protein was identified as a component of the protein complex that assembles at strong promoters. We demonstrate that AidB protein preferentially binds to UP elements, AT rich transcription enhancer sequences found upstream of many highly expressed genes, several DNA repair genes, and housekeeping genes. AidB allows efficient transcription from promoters containing an UP element upon exposure to a DNA methylating agent and protects downstream genes from DNA damage. The DNA binding domain is required to target AidB to specific genes preferentially protecting them from alkylation damage. However, deletion of AidB's DNA binding domain does not prevent its antimutagenic activity, instead this deletion appears to allow AidB to function as a cytoplasmic alkylation resistance protein. Our studies identify the role of AidB in alkylating agent exposed cells and suggest a new cellular strategy in which a subset of the genome is preferentially protected from damage by alkylating agents.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rippa
authors.forename: Angela
authors.initials: A
authors.lastname: Duilio
authors.forename: Pamela
authors.initials: P
authors.lastname: di Pasquale
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.forename: Paolo
authors.initials: P
authors.lastname: Landini
authors.forename: Michael R
authors.initials: MR
authors.lastname: Volkert
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000478:Alkylation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C090096:AidB protein, E coli; D000477:Alkylating Agents; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins