Base composition of mononucleotide runs affects DNA polymerase slippage and removal of frameshift intermediates by mismatch repair in Saccharomyces cerevisiae.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Gragg, H; Harfe, BD; Jinks-Robertson, S
Published Date
- December 2002
Published In
Volume / Issue
- 22 / 24
Start / End Page
- 8756 - 8762
PubMed ID
- 12446792
Pubmed Central ID
- PMC139878
International Standard Serial Number (ISSN)
- 0270-7306
Digital Object Identifier (DOI)
- 10.1128/MCB.22.24.8756-8762.2002
Language
- eng
Conference Location
- United States