The effects of trinucleotide repeats found in human inherited disorders on palindrome inviability in Escherichia coli suggest hairpin folding preferences in vivo.

Genetics
J M Darlow, D R Leach

Abstract

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).d(CTG) repeats inhibit plaque formation more than do odd numbers. Both d(CAG)2.d(CTG)2 and d(CGG)2.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).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.

Citations

Jul 2, 1999·Genetics·J K Schweitzer, D M Livingston
Jun 30, 2004·Journal of Molecular Biology·Gracjan Michlewski, Wlodzimierz J Krzyzosiak
Aug 28, 2002·The Journal of Biological Chemistry·Michael J HartenstineJohn Petruska
Jul 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·Z H ZhouM Jasin
Apr 3, 2002·Journal of Biosciences·Richard R SindenLuda S Shlyakhtenko
Dec 1, 1996·Molecular and Cellular Biology·D J MaurerD M Livingston
Sep 3, 1999·The Journal of Biological Chemistry·T Lyons-Darden, M D Topal
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·R S HansenS M Gartler
Apr 1, 1997·Molecular and Cellular Biology·C H FreudenreichV A Zakian
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·H MooreT D Petes
Feb 6, 1998·Journal of Molecular Biology·J M Darlow, D R Leach
Jun 22, 2002·The Journal of Biological Chemistry·Philip PinheiroJames A McClellan
Jan 29, 2000·Molecular Microbiology·K H SchmidtD R Leach
Jul 30, 2002·Computers & Chemistry·David UsseryAnders Krogh
Feb 15, 2000·Research in Microbiology·G F RichardB Dujon
Nov 26, 2010·The Journal of Gene Medicine·Yuji Nishikawa, Tomoyasu Sugiyama
Oct 6, 1999·Genome Research·L N BullN B Freimer

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.