title: Binding of DNA with Abf2p Increases Efficiency of DNA Uptake by Isolated Mitochondria.
abstract: Mutations in mitochondrial DNA often lead to severe hereditary diseases that are virtually resistant to symptomatic treatment. During the recent decades, many efforts were made to develop gene therapy approaches for treatment of such diseases using nucleic acid delivery into the organelles. The possibility of DNA import into mitochondria has been shown, but this process has low efficiency. In the present work, we demonstrate that the efficiency of DNA import can be significantly increased by preforming its complex with a mitochondria-targeted protein nonspecifically binding with DNA. As a model protein, we used the yeast protein Abf2p. In addition, we measured the length of the DNA site for binding this protein and the dissociation constant of the corresponding DNA-protein complex. Our data can serve as a basis for development of novel, highly efficient approaches for suppressing mutations in the mitochondrial genome.
authors.affiliation: Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia. kamenski_pa@mail.bio.msu.ru.
authors.forename: E O
authors.initials: EO
authors.lastname: Samoilova
authors.forename: I A
authors.initials: IA
authors.lastname: Krasheninnikov
authors.forename: E N
authors.initials: EN
authors.lastname: Vinogradova
authors.forename: P A
authors.initials: PA
authors.lastname: Kamenski
authors.forename: S A
authors.initials: SA
authors.lastname: Levitskii
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C072843:ABF2 protein, S cerevisiae; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C517609:TrxA protein, E coli; D013879:Thioredoxins; D004247:DNA