Nucleic Acids Research, Vol 27, Issue 11 2235-2240, Copyright © 1999 by Oxford University Press
T Lyons-Darden and MD Topal
The human genome contains many simple tandem repeats that are widely
dispersed and highly polymorphic. At least one group of simple tandem
repeats, the DNA trinucleotide repeats, can dramaticallyexpand in size
during transmission from one generation to the next to cause disease by a
process known as dynamic mutation. We investigated the ability of
trinucleotide repeats AAT and CAG to expand in size during DNA replication
using a minimal in vitro system composed of the repeat tract, with and
without unique flanking sequences, and DNA polymerase. Varying
Mg2+concentration and temperature gave dramatic expansions of repeat size
during DNA replication in vitro. Expansions of up to 1000- fold were
observed. Mismatches partially stabilized the repeat tracts against
expansion. Expansions were only detected when the primer was complementary
to the repeat tract rather than the flanking sequence. The results imply
that cellular environment and whether the growing strand contains a nick or
gap are important factors for the expansion process in vivo.
ARTICLES
Effects of temperature, Mg2+ concentration and mismatches on triplet- repeat expansion during DNA replication in vitro
Lineberger Comprehensive Cancer Center and Department of Pathology, University of North Carolina Medical School, Chapel Hill, NC 27599- 7295, USA.
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