SwePub
Sök i LIBRIS databas

  Extended search

WFRF:(Good Peter J)
 

Search: WFRF:(Good Peter J) > Disruption of Highe...

  • Bergquist, HelenUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden. (author)

Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)(n) Repeats by PNA or LNA Targeting

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-11-15
  • PLOS,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-199545
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-199545URI
  • https://doi.org/10.1371/journal.pone.0165788DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:134728853URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312088URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20170116
  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Rocha, Cristina S. J.Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden. (author)
  • Alvarez-Asencio, RubenKTH,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.(Swepub:kth)u1u6jl5f (author)
  • Nguyen, Chi-Hung (author)
  • Rutland, Mark W.KTH,Kemi,KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, Stockholm, Sweden.(Swepub:kth)u1ml9bxf (author)
  • Smith, C. I. EdvardKarolinska Institutet,Karolinska Inst, Dept Lab Med, Clin Res Ctr, SE-14186 Huddinge, Sweden. (author)
  • Good, LiamUniv London, Dept Pathol & Infect Dis, Royal Vet Coll, London WC1E 7HU, England. (author)
  • Nielsen, Peter E.Univ Copenhagen, Panum Inst, Fac Hlth & Med Sci, Dept Cellular & Mol Med, Copenhagen, Denmark. (author)
  • Zain, RulaKarolinska 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. (author)
  • Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Related titles

  • In:PLOS ONE: PLOS11:111932-6203

Internet link

Find in a library

  • PLOS ONE (Search for host publication in LIBRIS)

To the university's database

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view