Disease relevance of MSH1

• The MSH1 and MSH2 genes of Saccharomyces cerevisiae are predicted to encode proteins that are homologous to the Escherichia coli MutS and Streptococcus pneumoniae HexA proteins and their homologs [1].

High impact information on MSH1

• In addition, an msh1 mutation destabilized poly(GT) tracts in the mitochondrial genome [2].
• The yeast Saccharomyces cerevisiae encodes six proteins, Msh1p to Msh6p, that show strong amino acid sequence similarity to MutS, a central component of the bacterial mutHLS mismatch repair system [3].
• The effect of DNA mismatches on the ATPase activity of MSH1, a protein in yeast mitochondria that recognizes DNA mismatches [4].
• In this study, p3 show that DNA alters the pH dependence of the MSH1 ATPase and stimulates ATP hydrolysis at neutral pH [4].
• Purification and characterization of MSH1, a yeast mitochondrial protein that binds to DNA mismatches [5].

Biological context of MSH1

• Disruption of the MSH1 gene caused a petite phenotype which was established rapidly [1].
• In contrast, transcription of the MSH1, MSH3 and MLH1 genes was not regulated during the cell cycle [6].
• The yeast MSH1 gene is not involved in DNA repair or recombination during meiosis [7].
• Overlapping contributions of Msh1p and putative recombination proteins Cce1p, Din7p, and Mhr1p in large-scale recombination and genome sorting events in the mitochondrial genome of Saccharomyces cerevisiae [8].
• The specific binding of MSH1 to mismatches is more resistant to NaCl inhibition and has a slower dissociation rate as compared to the nonspecific binding to complementary DNA sequences [5].

Anatomical context of MSH1

• The MSH1 gene, which is thought to be involved in DNA mismatch repair in mitochondria, was also not induced under aerobic growth conditions [6].

Associations of MSH1 with chemical compounds

• MSH1 exhibits an ATPase activity that hydrolyses approximately 1 ATP molecule/min in the absence of DNA [4].
• Here, we report that moderate overexpression of the msh1-R813W or msh1-G776D allele, in strains which also carry the wild-type MSH1 allele, slightly increases the frequency of mutations conferring resistance to erythromycin (E(r)) and elevates the frequency of alterations within a polyGT tract present in mitochondrial DNA (mtDNA) [9].
• 4',6-Diamidino-2-phenylindole (DAPI) staining of msh1 yeast revealed an aberrant distribution of mtDNA [1].
• Finally, we also show that the increased frequency of Olir mutants arising in an msh1/MSH1 heterozygote grown in glucose-containing medium is further enhanced if the cells are cultivated in glycerol-containing medium, i.e. under conditions when the respiratory chain is fully active [10].

Other interactions of MSH1

• These results indicate that MSH1 plays a role in repair or stability of mtDNA and MSH2 plays a role in repair of 4-bp insertion/deletion mispairs in the nucleus [1].
• We show that the G776D and F105A alleles of MSH1 exhibit no defects in meiotic recombination, repair base-base mismatches and large loop mismatches efficiently during meiosis, and have high levels of spore viability [7].

References