HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 8, 6444-6454, February 20, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/8/6444    most recent M309596200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Napierala, M. Articles by Wells, R. D. Search for Related Content PubMed PubMed Citation Articles by Napierala, M. Articles by Wells, R. D. Social Bookmarking                      What's this?

Structure-dependent Recombination Hot Spot Activity of GAA·TTC Sequences from Intron 1 of the Friedreich's Ataxia Gene^*

Marek Napierala, Ruhee Dere, Alexandre Vetcher, and Robert D. Wells

From the Institute of Biosciences and Technology, Center for Genome Research, Texas A&M University System Health Science Center, Texas Medical Center, Houston, Texas 77030-3303

The recombinational properties of long GAA·TTC repeating sequences were analyzed in Escherichia coli to gain further insights into the molecular mechanisms of the genetic instability of this tract as possibly related to the etiology of Friedreich's ataxia. Intramolecular and intermolecular recombination studies showed that the frequency of recombination between the GAA·TTC tracts was as much as 15 times higher than the non-repeating control sequences. Homologous, intramolecular recombination between GAA·TTC tracts and GAAGGA·TCCTTC repeats also occurred with a very high frequency (0.8%). Biochemical analyses of the recombination products demonstrated the expansions and deletions of the GAA·TTC repeats. These results, together with our previous studies on the CTG·CAG sequences, suggest that the recombinational hot spot characteristics may be a common feature of all triplet repeat sequences. Unexpectedly, we found that the recombination properties of the GAA·TTC tracts were unique, compared with CTG·CAG repeats, because they depended on the DNA secondary structure polymorphism. Increasing the length of the GAA·TTC repeats decreased the intramolecular recombination frequency between these tracts. Also, a correlation was found between the propensity of the GAA·TTC tracts to adopt the sticky DNA conformation and the inhibition of intramolecular recombination. The use of novobiocin to modulate the intracellular DNA topology, i.e. the lowering of the negative superhelical density, repressed the formation of the sticky DNA structure, thereby restoring the expected positive correlation between the length of the GAA·TTC tracts and the frequency of intramolecular recombination. Hence, our results demonstrate that sticky DNA exists and functions in E. coli.

Received for publication, August 28, 2003 , and in revised form, November 17, 2003.

^* This work was supported by National Institutes of Health Grants NS37554 and ES11347, the Robert A. Welch Foundation, and the Friedreich's Ataxia Research Alliance. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Molecular and Cell Biology, the University of Texas at Dallas, Mail Station F03.1, Richardson, TX 75083.

To whom correspondence should be addressed: Center for Genome Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, 2121 W. Holcombe Blvd. Houston, TX 77030-3303. Tel.: 713-677-7651; Fax: 713-677-7689; E-mail: rwells{at}ibt.tamu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Brandstrom, A. T. Bagshaw, N. J. Gemmell, and H. Ellegren The Relationship Between Microsatellite Polymorphism and Recombination Hot Spots in the Human Genome Mol. Biol. Evol., December 1, 2008; 25(12): 2579 - 2587. [Abstract] [Full Text] [PDF]

				R. D. Wells DNA triplexes and Friedreich ataxia FASEB J, June 1, 2008; 22(6): 1625 - 1634. [Abstract] [Full Text] [PDF]

				A. Entezam and K. Usdin ATR protects the genome against CGG{middle dot}CCG-repeat expansion in Fragile X premutation mice Nucleic Acids Res., February 11, 2008; 36(3): 1050 - 1056. [Abstract] [Full Text] [PDF]

				L. M. Pollard, R. L. Bourn, and S. I. Bidichandani Repair of DNA double-strand breaks within the (GAA*TTC)n sequence results in frequent deletion of the triplet-repeat sequence Nucleic Acids Res., February 2, 2008; 36(2): 489 - 500. [Abstract] [Full Text] [PDF]

				L. M. Pollard, Y. K. Chutake, P. M. Rindler, and S. I. Bidichandani Deficiency of RecA-dependent RecFOR and RecBCD pathways causes increased instability of the (GAA{middle dot}TTC)n sequence when GAA is the lagging strand template Nucleic Acids Res., November 29, 2007; 35(20): 6884 - 6894. [Abstract] [Full Text] [PDF]

				P. M. Rindler, R. M. Clark, L. M. Pollard, I. De Biase, and S. I. Bidichandani Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats Nucleic Acids Res., December 4, 2006; 34(21): 6352 - 6361. [Abstract] [Full Text] [PDF]

				R. Burnett, C. Melander, J. W. Puckett, L. S. Son, R. D. Wells, P. B. Dervan, and J. M. Gottesfeld DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA{middle dot}TTC repeats in Friedreich's ataxia PNAS, August 1, 2006; 103(31): 11497 - 11502. [Abstract] [Full Text] [PDF]

				A. Bacolla, J. R. Collins, B. Gold, N. Chuzhanova, M. Yi, R. M. Stephens, S. Stefanov, A. Olsh, J. P. Jakupciak, M. Dean, et al. Long homopurine*homopyrimidine sequences are characteristic of genes expressed in brain and the pseudoautosomal region. Nucleic Acids Res., January 1, 2006; 34(9): 2663 - 2675. [Abstract] [Full Text] [PDF]

				R. D. Wells, R. Dere, M. L. Hebert, M. Napierala, and L. S. Son Advances in mechanisms of genetic instability related to hereditary neurological diseases Nucleic Acids Res., July 8, 2005; 33(12): 3785 - 3798. [Abstract] [Full Text] [PDF]

				M. Wojciechowska, A. Bacolla, J. E. Larson, and R. D. Wells The Myotonic Dystrophy Type 1 Triplet Repeat Sequence Induces Gross Deletions and Inversions J. Biol. Chem., January 14, 2005; 280(2): 941 - 952. [Abstract] [Full Text] [PDF]

				A. Bacolla and R. D. Wells Non-B DNA Conformations, Genomic Rearrangements, and Human Disease J. Biol. Chem., November 12, 2004; 279(46): 47411 - 47414. [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]