title: Mismatch recognition function of Arabidopsis thaliana MutSγ.
abstract: Genetic stability depends in part on an efficient DNA lesion recognition and correction by the DNA mismatch repair (MMR) system. In eukaryotes, MMR is initiated by the binding of heterodimeric MutS homologue (MSH) complexes, MSH2-MSH6 and MSH2-MSH3, which recognize and bind mismatches and unpaired nucleotides. Plants encode another mismatch recognition protein, named MSH7. MSH7 forms a heterodimer with MSH2 and the protein complex is designated MutSγ. We here report the effect the expression of Arabidopsis MSH2 and MSH7 alone or in combination exert on the genomic stability of Saccharomyces cerevisiae. AtMSH2 and AtMutSγ proteins failed to complement the hypermutator phenotype of an msh2 deficient strain. However, overexpressing AtMutSγ in MMR proficient strains generated a 4-fold increase in CAN1 forward mutation rate, when compared to wild-type strains. Can(r) mutation spectrum analysis of AtMutSγ overproducing strains revealed a substantial increase in the frequency of base substitution mutations, including an increased accumulation of base pair changes from G:C to A:T and T:A to C:G, G:C or A:T. Taken together, these results suggest that AtMutSγ affects yeast genomic stability by recognizing specific mismatches and preventing correction by yeast MutSα and MutSβ, with subsequent inability to interact with yeast downstream proteins needed to complete MMR.
authors: Centro de Estudios Fotosintéticos y Bioquímicos CEFOBI, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: Rodrigo
authors: R
authors: Gómez
authors: Claudia P
authors: CP
authors: Spampinato
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D015870:Gene Expression; D005816:Genetic Complementation Test; D016681:Genome, Fungal; D042822:Genomic Instability; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D059645:Mutation Rate; D020125:Mutation, Missense; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D026923:Amino Acid Transport Systems, Basic; D029681:Arabidopsis Proteins; C502212:CAN1 protein, S cerevisiae; C499543:MSH7 protein, Arabidopsis; D029701:Saccharomyces cerevisiae Proteins; C108984:MSH2 protein, Arabidopsis; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein