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Science 6 February 1998:
Vol. 279. no. 5352, pp. 853 - 856
DOI: 10.1126/science.279.5352.853
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Reports

Expansion and Length-Dependent Fragility of CTG Repeats in Yeast

Catherine H. Freudenreich, Sara M. Kantrow, Virginia A. Zakian *

Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
*   To whom correspondence should be addressed. E-mail: vzakian{at}molecular.princeton.edu

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J. M. Kirchner, H. Tran, and M. A. Resnick (2000)
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M. J. Ireland, S. S. Reinke, and D. M. Livingston (2000)
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DNA Polymerase III Proofreading Mutants Enhance the Expansion and Deletion of Triplet Repeat Sequences in Escherichia coli.
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CGG/CCG repeats exhibit orientation-dependent instability and orientation-independent fragility in Saccharomyces cerevisiae.
B. S. Balakumaran, C. H. Freudenreich, and V. A. Zakian (2000)
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The RAD2 Domain of Human Exonuclease 1 Exhibits 5' to 3' Exonuclease and Flap Structure-specific Endonuclease Activities.
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Saccharomyces cerevisiae RNase H(35) Functions in RNA Primer Removal during Lagging-Strand DNA Synthesis, Most Efficiently in Cooperation with Rad27 Nuclease.
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P. J. White, R. H. Borts, and M. C. Hirst (1999)
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L. K. Lewis, J. W. Westmoreland, and M. A. Resnick (1999)
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Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae.
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J. Biol. Chem. 274, 14602-14608
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DNA secondary structure: A common and causative factor for expansion in human disease.
C. T. McMurray (1999)
PNAS 96, 1823-1825
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A role for FEN-1 in nonhomologous DNA end joining: The order of strand annealing and nucleolytic processing events.
X. Wu, T. E. Wilson, and M. R. Lieber (1999)
PNAS 96, 1303-1308
   Abstract »    Full Text »    PDF »
Triplet repeats form secondary structures that escape DNA repair in yeast.
H. Moore, P. W. Greenwell, C.-P. Liu, N. Arnheim, and T. D. Petes (1999)
PNAS 96, 1504-1509
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Structural Changes Measured by X-ray Scattering from Human Flap Endonuclease-1 Complexed with Mg2+ and Flap DNA Substrate.
C.-Y. Kim, B. Shen, M. S. Park, and G. A. Olah (1999)
J. Biol. Chem. 274, 1233-1239
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Partial Functional Deficiency of E160D Flap Endonuclease-1 Mutant in Vitro and in Vivo Is Due to Defective Cleavage of DNA Substrates.
G. Frank, J. Qiu, M. Somsouk, Y. Weng, L. Somsouk, J. P. Nolan, and B. Shen (1998)
J. Biol. Chem. 273, 33064-33072
   Abstract »    Full Text »    PDF »


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