Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich's ataxia

Mol Cell. 1999 Apr;3(4):465-75. doi: 10.1016/s1097-2765(00)80474-8.

Abstract

A novel DNA structure, sticky DNA, is described for lengths of (GAA.TTC)n found in intron 1 of the frataxin gene of Friedreich's ataxia patients. Sticky DNA is formed by the association of two purine.purine.pyrimidine (R.R.Y) triplexes in negatively supercoiled plasmids at neutral pH. An excellent correlation was found between the lengths of (GAA.TTC) (> 59 repeats): first, in FRDA patients, second, required to inhibit transcription in vivo and in vitro, and third, required to adopt the sticky conformation. Fourth, (GAAGGA.TCCTTC)65, also found in intron 1, does not form sticky DNA, inhibit transcription, or associate with the disease. Hence, R.R.Y triplexes and/or sticky DNA may be involved in the etiology of FRDA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA / genetics*
  • DNA / ultrastructure
  • DNA, Superhelical / genetics
  • DNA, Superhelical / ultrastructure
  • Electrophoresis, Agar Gel
  • Friedreich Ataxia / etiology
  • Friedreich Ataxia / genetics*
  • Humans
  • Iron-Binding Proteins*
  • Microscopy, Electron
  • Models, Molecular
  • Nucleic Acid Conformation
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic

Substances

  • DNA, Superhelical
  • Iron-Binding Proteins
  • frataxin
  • triplex DNA
  • DNA
  • Phosphotransferases (Alcohol Group Acceptor)