title: PNA binding to the non-template DNA strand interferes with transcription, suggesting a blockage mechanism mediated by R-loop formation.
abstract: Peptide Nucleic Acids (PNAs) are artificial DNA mimics with superior nucleic acid binding capabilities. T7 RNA polymerase (T7 RNAP) transcription upon encountering PNA bound to the non-template DNA strand was studied in vitro. A characteristic pattern of blockage signals was observed, extending downstream from the PNA binding site, similar to that produced by G-rich homopurine-homopyrimidine (hPu-hPy) sequences and likely caused by R-loop formation. Since blocked transcription complexes in association with stable R-loops may interfere with replication and in some cases trigger apoptosis, targeted R-loop formation might be employed to inactivate selected cells, such as those in tumors, based upon their unique complement of expressed genes.
authors.affiliation: Department of Biology, Stanford University, Stanford, California.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Belotserkovskii
authors.affiliation: Department of Biology, Stanford University, Stanford, California.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hanawalt
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics
chemical_list: D020135:Peptide Nucleic Acids; D014764:Viral Proteins; D004247:DNA; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases
keywords: R-loop toxicity; RNA-DNA hybrids; gene targeting; transcription blockage; triplex