Sökning: WFRF:(Good Peter J) > Disruption of Highe...
Fältnamn | Indikatorer | Metadata |
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000 | 05078naa a2200529 4500 | |
001 | oai:DiVA.org:kth-199545 | |
003 | SwePub | |
008 | 170109s2016 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:134728853 | |
009 | oai:DiVA.org:uu-312088 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-1995452 URI |
024 | 7 | a https://doi.org/10.1371/journal.pone.01657882 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1347288532 URI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3120882 URI |
040 | a (SwePub)kthd (SwePub)kid (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Bergquist, Helenu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden.4 aut |
245 | 1 0 | a Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)(n) Repeats by PNA or LNA Targeting |
264 | c 2016-11-15 | |
264 | 1 | b PLOS,c 2016 |
338 | a print2 rdacarrier | |
500 | a QC 20170116 | |
520 | a Expansion of (GAA)(n) repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich's ataxia. (GAA)(n) expansions form non-canonical structures, including intramolecular triplex (H-DNA), and Rloops and are associated with epigenetic modifications. With the aim of interfering with higher order H-DNA (like) DNA structures within pathological (GAA)(n) expansions, we examined sequence-specific interaction of peptide nucleic acid (PNA) with (GAA)(n) repeats of different lengths (short: n= 9, medium: n= 75 or long: n= 115) by chemical probing of triple helical and single stranded regions. We found that a triplex structure (H-DNA) forms at GAA repeats of different lengths; however, single stranded regions were not detected within the medium size pathological repeat, suggesting the presence of a more complex structure. Furthermore, (GAA) 4-PNA binding of the repeat abolished all detectable triplex DNA structures, whereas (CTT) 5-PNA did not. We present evidence that (GAA) 4-PNA can invade the DNA at the repeat region by binding the DNA CTT strand, thereby preventing non-canonical-DNA formation, and that triplex invasion complexes by (CTT) 5-PNA form at the GAA repeats. Locked nucleic acid (LNA) oligonucleotides also inhibited triplex formation at GAA repeat expansions, and atomic force microscopy analysis showed significant relaxation of plasmid morphology in the presence of GAA-LNA. Thus, by inhibiting disease related higher order DNA structures in the Frataxin gene, such PNA and LNA oligomers may have potential for discovery of drugs aiming at recovering Frataxin expression. | |
650 | 7 | a NATURVETENSKAPx Biologix Genetik0 (SwePub)106092 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Genetics0 (SwePub)106092 hsv//eng |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
700 | 1 | a Rocha, Cristina S. J.u Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden.4 aut |
700 | 1 | a Alvarez-Asencio, Rubenu KTH,Kemi,Universitario de Cantoblanco, Spain,KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, Stockholm, Sweden.;Fdn IMDEA Nanociencia, 9 Campus Univ Cantoblanco, Madrid, Spain.4 aut0 (Swepub:kth)u1u6jl5f |
700 | 1 | a Nguyen, Chi-Hung4 aut |
700 | 1 | a Rutland, Mark W.u KTH,Kemi,KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, Stockholm, Sweden.4 aut0 (Swepub:kth)u1ml9bxf |
700 | 1 | a Smith, C. I. Edvardu Karolinska Institutet,Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden.4 aut |
700 | 1 | a Good, Liamu Univ London, Dept Pathol & Infect Dis, Royal Vet Coll, London WC1E 7HU, England.4 aut |
700 | 1 | a Nielsen, Peter E.u Univ Copenhagen, Panum Inst, Fac Hlth & Med Sci, Dept Cellular & Mol Med, Copenhagen, Denmark.4 aut |
700 | 1 | a Zain, Rulau Karolinska Institutet,Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Ctr Rare Dis, SE-17176 Stockholm, Sweden.4 aut |
710 | 2 | a Uppsala universitetb Institutionen för medicinsk biokemi och mikrobiologi4 org |
773 | 0 | t PLOS ONEd : PLOSg 11:11q 11:11x 1932-6203 |
856 | 4 | u https://doi.org/10.1371/journal.pone.0165788y Fulltext |
856 | 4 | u https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0165788&type=printable |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1071236/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-199545 |
856 | 4 8 | u https://doi.org/10.1371/journal.pone.0165788 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:134728853 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312088 |
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