Harrington JM and Kolodner RD (2007) Saccharomyces cerevisiae Msh2-Msh3 acts in repair of base-base mispairs. Mol Cell Biol 27(18):6546-54
Abstract: DNA mismatch repair is thought to act through two sub-pathways involving recognition of base:base and insertion/deletion mispairs by the Msh2-Msh6 heterodimer and recognition of insertion/deletion mispairs by the Msh2-Msh3 heterodimer. Here, through genetic and biochemical approaches, we describe a previously unidentified role of the Msh2-Msh3 heterodimer in the recognition of base:base mispairs and the suppression of homology-mediated duplication and deletion mutations. S. cerevisiae msh3 mutants did not show an increase in the rate of base substitution mutations in the CAN1 forward mutation assay compared to wild-type but did show an altered spectrum of base substitution mutations including increased accumulation of GC bp to CG bp and AT bp to TA bp changes; msh3 mutants also accumulated homology-mediated duplication and deletion mutations. The mutation spectrum of mlh3 mutants paralleled that of msh3 mutants suggesting that the Mlh1-Mlh3 heterodimer may also play a role in repair of base:base mispairs and in suppression of homology-mediated duplication and deletion mutations. Mispair binding analysis with purified Msh2-Msh3 and DNA substrates derived from CAN1 sequences found to be mutated in vivo demonstrated that Msh2-Msh3 exhibited robust binding to specific base:base mispairs that was consistent with functional mispair binding.
|Status: Published||Type: Journal Article||PubMed ID: 17636021|
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