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J. Biol. Chem., Vol. 275, Issue 37, 28386-28397, September 15, 2000
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From the Institute of Biosciences and Technology, Center for Genome
Research, Texas A&M University, Texas Medical Center,
Houston, Texas 77030
Triplet repeat sequence (TRS) inserts containing
(CTG·CAG)n (17-175 units in length) were tandemly duplicated
when propagated in plasmids in Escherichia coli. The
products of this novel type of TRS genetic instability are tracts of as
many as 34 multiple units, which contain the entire TRS as well as 129 base pairs of nonrepetitive flanking sequence. The duplication process required the presence of two or more TRS-containing units. Close proximity (170 base pairs) of the TRS to the R6K
Tandem Duplication
A NOVEL TYPE OF TRIPLET REPEAT INSTABILITY*
, and
origin of
replication of the pUTminiTn5Cm-derived constructs stimulated the
tandem duplication process. These events are proposed to occur due to
secondary structure formation, stalling of DNA synthesis, and
slippage-mediated misalignment of the complementary strands relative to
each other during DNA replication. This mechanism may account for the
TRS-associated duplications in protein kinase and metalloprotease genes
in neuroblastomas and melanomas, as well as the massive repeat
expansions in type II triplet repeat neurological diseases.
*
This research was supported by National Institutes of Health
Grants GM52982 and NS37554 and by the Robert A. Welch Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Center of Microbiology and Virology, Polish
Academy of Sciences, 106 Lodowa Str., 93-232 Lodz, Poland.
§
To whom correspondence should be addressed: Center for Genome
Research, Institute of Biosciences and Technology, Texas A&M University, Texas Medical Center, 2121 Holcombe Blvd. Houston, TX 77030-3303. Tel.: 713-677-7651; Fax: 713-677-7689; E-mail: rwells@ibt.tamu.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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