Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6 gene.
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.
Hess
Martin T
MT
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.
Mendillo
Marc L
ML
Mazur
Dan J
DJ
Kolodner
Richard D
RD
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
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