- THIS ARTICLE
- Full Text (PDF)
- Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Darlow, J. M.
- Articles by Leach, DRF.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Darlow, J. M.
- Articles by Leach, DRF.
Genetics, Vol 141, 825-832, Copyright © 1995
INVESTIGATIONS |
The Effects of Trinucleotide Repeats Found in Human Inherited Disorders on Palindrome Inviability in Escherichia coli Suggest Hairpin Folding Preferences In Vivo
J. M. Darlow and DRF. Leach
Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom
Unusual DNA secondary structures have been implicated in the expansion of trinucleotide repeat tracts that are associated with several human inherited disorders. We present evidence consistent with the folding of these trinucleotide repeats into hairpin loops at the center of a long DNA palindrome in vivo. Our assay utilizes a palindrome in bacteriophage {lambda}, the center of which determines its ability to inhibit plaque formation in a manner that is consistent with folding into a hairpin or cruciform structure. We show that central inserts of even numbers of d(CAG){middot}d(CTG) repeats inhibit plaque formation more than do odd numbers. Both d(CAG)(2){middot}d(CTG)(2) and d(CGG)(2){middot}d(CCG)(2) central sequences behave like DNA sequences known to form two-base loops in vitro, suggesting that they may also form compact and stable loops. By contrast, repeats of d(GAC){middot}d(GTC) do not show any evidence consistent with unusual loop stability. These results agree with in vitro evidence that the unstable repeats can form hairpin secondary structures and suggest a favored position of folding. We discuss the potential roles of secondary structures, DNA replication and recombination in models of repeat tract expansion.
This article has been cited by other articles:
 |
|
 |
|
  R. Zahra, J. K. Blackwood, J. Sales, and D. R. F. Leach Proofreading and Secondary Structure Processing Determine the Orientation Dependence of CAG{middle dot}CTG Trinucleotide Repeat Instability in Escherichia coli Genetics, May 1, 2007; 176(1): 27 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Chi and S. L. Lam Structural roles of CTG repeats in slippage expansion during DNA replication Nucleic Acids Res., March 14, 2005; 33(5): 1604 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. I. Hashem, M. J. Pytlos, E. A. Klysik, K. Tsuji, M. Khajav, T. Ashizawa, and R. R. Sinden Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients Nucleic Acids Res., December 1, 2004; 32(21): 6334 - 6346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dere, M. Napierala, L. P. W. Ranum, and R. D. Wells Hairpin Structure-forming Propensity of the (CCTG{middle dot}CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2 J. Biol. Chem., October 1, 2004; 279(40): 41715 - 41726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Meservy, R. G. Sargent, R. R. Iyer, F. Chan, G. J. McKenzie, R. D. Wells, and J. H. Wilson Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells Mol. Cell. Biol., May 1, 2003; 23(9): 3152 - 3162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Hartenstine, M. F. Goodman, and J. Petruska Weak Strand Displacement Activity Enables Human DNA Polymerase beta to Expand CAG/CTG Triplet Repeats at Strand Breaks J. Biol. Chem., October 25, 2002; 277(44): 41379 - 41389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pinheiro, G. Scarlett, A. Rodger, P. M. Rodger, A. Murray, T. Brown, S. F. Newbury, and J. A. McClellan Structures of CUG Repeats in RNA. POTENTIAL IMPLICATIONS FOR HUMAN GENETIC DISEASES J. Biol. Chem., September 13, 2002; 277(38): 35183 - 35190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-H. Zhou, E. Akgun, and M. Jasin Repeat expansion by homologous recombination in the mouse germ line at palindromic sequences PNAS, July 17, 2001; 98(15): 8326 - 8333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lyons-Darden and M. D. Topal Abasic Sites Induce Triplet-repeat Expansion during DNA Replication in Vitro J. Biol. Chem., September 10, 1999; 274(37): 25975 - 25978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. N. Bull, C. R. Pabón-Peña, and N. B. Freimer Compound Microsatellite Repeats: Practical and Theoretical Features Genome Res., September 1, 1999; 9(9): 830 - 838. [Abstract] [Full Text]
|
|
|
|
|
|
J. K. Schweitzer and D. M. Livingston The Effect of DNA Replication Mutations on CAG Tract Stability in Yeast Genetics, July 1, 1999; 152(3): 953 - 963. [Abstract] [Full Text]
|
|
|
|
|
|
H. Moore, P. W. Greenwell, C.-P. Liu, N. Arnheim, and T. D. Petes Triplet repeats form secondary structures that escape DNA repair in yeast PNAS, February 16, 1999; 96(4): 1504 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. DeMarini, M. L. Shelton, A. Abu-Shakra, A. Szakmary, and J. G. Levine Spectra of Spontaneous Frameshift Mutations at the hisD3052 Allele of Salmonella typhimurium in Four DNA Repair Backgrounds Genetics, May 1, 1998; 149(1): 17 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Petruska, M. J. Hartenstine, and M. F. Goodman Analysis of Strand Slippage in DNA Polymerase Expansions of CAG/CTG Triplet Repeats Associated with Neurodegenerative Disease J. Biol. Chem., February 27, 1998; 273(9): 5204 - 5210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Hansen, T. K. Canfield, A. D. Fjeld, S. Mumm, C. D. Laird, and S. M. Gartler A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication PNAS, April 29, 1997; 94(9): 4587 - 4592. [Abstract] [Full Text] [PDF]
|
|