title: Requirement of the yeast MSH3 and MSH6 genes for MSH2-dependent genomic stability.
abstract: Defects in DNA mismatch repair result in instability of simple repetitive DNA sequences and elevated levels of spontaneous mutability. The human G/T mismatch binding protein, GTBP/p160, has been suggested to have a role in the repair of base-base and single nucleotide insertion-deletion mismatches. Here we examine the role of the yeast GTBP homolog, MSH6, in mismatch repair. We show that both MSH6 and MSH3 genes are essential for normal genomic stability. Interestingly, although mutations in either MSH3 or MSH6 do not cause the extreme microsatellite instability and spontaneous mutability observed in the msh2 mutant, yeast cells harboring null mutations in both the MSH3 and MSH6 genes exhibit microsatellite instability and mutability similar to that in the msh2 mutant. Results from epistasis analyses indicate that MSH2 functions in mismatch repair in conjunction with MSH3 or MSH6 and that MSH3 and MSH6 constitute alternate pathways of MSH2-dependent mismatch repair.
authors.affiliation: Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, 77555-1061, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Johnson
authors.forename: G K
authors.initials: GK
authors.lastname: Kovvali
authors.forename: L
authors.initials: L
authors.lastname: Prakash
authors.forename: S
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000595:Amino Acid Sequence; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D017353:Gene Deletion; D005800:Genes, Fungal; D016681:Genome, Fungal; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D012091:Repetitive Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C081696:MSH3 protein, S cerevisiae; C098790:MSH6 protein, S cerevisiae; D000074081:MutS Homolog 3 Protein; D029701:Saccharomyces cerevisiae Proteins; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein