title: Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6 gene.
abstract: Here, the ATP-binding, ATP hydrolysis, mispair-binding, sliding clamp formation, and Mlh1-Pms1 complex interaction properties of dominant mutant Msh2-Msh6 complexes have been characterized. The results demonstrate two mechanisms for dominance. In one, seen with the Msh6-S1036P and Msh6-G1067D mutant complexes, the mutant complex binds mispaired bases, is defective for ATP-induced sliding clamp formation and assembly of ternary complexes with Mlh1-Pms1, and occludes mispaired bases from other mismatch repair pathways. In the second, seen with the Msh6-G1142D complex, the mutant complex binds mispaired bases and is defective for ATP-induced sliding clamp formation but assembles ternary complexes with Mlh1-Pms1 that either occlude the mispaired base or prevent Mlh1-Pms1 from acting in alternate mismatch repair pathways.
authors.affiliation: Department of Medicine, Cancer Center, Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Hess
authors.forename: Marc L
authors.initials: ML
authors.lastname: Mendillo
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Mazur
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005799:Genes, Dominant; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; C098790:MSH6 protein, S cerevisiae; C088858:PMS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein