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Molecular and Cellular Biology, December 2002, p. 8756-8762, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8756-8762.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Base Composition of Mononucleotide Runs Affects DNA Polymerase Slippage and Removal of Frameshift Intermediates by Mismatch Repair in Saccharomyces cerevisiae

Hana Gragg, Brian D. Harfe,{dagger} and Sue Jinks-Robertson*

Department of Biology, Emory University, Atlanta, Georgia 30322

Received 10 June 2002/ Returned for modification 9 July 2002/ Accepted 10 September 2002

The postreplicative mismatch repair (MMR) system is important for removing mutational intermediates that are generated during DNA replication, especially those that arise as a result of DNA polymerase slippage in simple repeats. Here, we use a forward mutation assay to systematically examine the accumulation of frameshift mutations within mononucleotide runs of variable composition in wild-type and MMR-defective yeast strains. These studies demonstrate that (i) DNA polymerase slippage occurs more often in 10-cytosine/10-guanine (10C/10G) runs than in 10-adenine/10-thymine (10A/10T) runs, (ii) the MMR system removes frameshift intermediates in 10A/10T runs more efficiently than in 10C/10G runs, (iii) the MMR system removes -1 frameshift intermediates more efficiently than +1 intermediates in all 10-nucleotide runs, and (iv) the repair specificities of the Msh2p-Msh3p and Msh2p-Msh6p mismatch recognition complexes with respect to 1-nucleotide insertion/deletion loops vary dramatically as a function of run composition. These observations are relevant to issues of genome stability, with both the rates and types of mutations that accumulate in mononucleotide runs being influenced by the primary sequence of the run as well as by the status of the MMR system.

* Corresponding author. Mailing address: Department of Biology, 1510 Clifton Rd., Emory University, Atlanta, GA 30322. Phone: (404) 727-6312. Fax: (404) 727-2880. E-mail: jinks{at}biology.emory.edu.

{dagger} Present address: Department of Genetics, Harvard Medical School, Boston, MA 02115.

Molecular and Cellular Biology, December 2002, p. 8756-8762, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8756-8762.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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