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Papers In Press, published online ahead of print April 3, 2000
Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA 90089-1340
Corresponding Author: mgoodman{at}mizar.usc.edu
Repetitions of CAG or CTG triplets in DNA can form intrastrand hairpin loops with combinations of normal and mismatched basepairs that easily rearrange. Such loops may promote primer/template slippage in DNA replication or repair to give triplet-repeat expansions like those associated with neurodegenerative diseases. Using self-priming sequences, e.g., (CAG)16(CTG)4, we resolve all hairpin loops formed and measure their slippage and expansion rates with DNA polymerase at 37 oC. Comparing CAG/CTG loop structures with GAC/GTC structures, having similar H-bonding but different base stacking, we find CAG, CTG and GTC triplets predominantly form even-membered loops that slip in steps of 2 triplets, whereas GAC triplets favor odd-numbered loops. Slippage rates decline as hairpin stability increases, supporting idea that slippage is easier in less stable regions. Loop stabilities (in low salt) increase in order GTC
J. Biol. Chem, 10.1074/jbc.M910272199
Submitted on December 23, 1999
Revised on March 29, 2000
Accepted on April 2, 2000
Base Stacking and Even/Odd Behavior of Hairpin Loops in DNA Triplet Repeat Sequences Undergoing Slippage and Expansion with DNA Polymerase
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