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The Escherichia coli MutHLS system has been highly conserved throughout evolution. The eukaryotic pathway results in a specialization of MutS homologs such as MSH2 that have evolved to play crucial roles in both DNA mismatch repair and meiotic recombination. In Saccharomyces cerevisiae, MSH4 is a meiosis-specific protein that is not involved in mismatch correction. This protein is required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis I.