High impact information on MIF2

• MIF2 is a unique sequence located 15 cM distal to HIS6 on chromosome IX that induces a high frequency of chromosome VII loss and a lower frequency of chromosome V loss when present in high copy number; it has no effect on mitotic recombination [1].
• Two DNA sequences that reduce mitotic fidelity of chromosome transmission have been identified: MIF1 and MIF2 [1].
• Disruption of the genomic MIF2 locus was lethal and cells lacking this function arrested division with a terminal phenotype characteristic of a block in DNA replication or nuclear division [1].
• Using in vivo cross-linking followed by immunoprecipitation, we show that the Mif2 protein of the budding yeast Saccharomyces cerevisiae, previously implicated in centromere function by genetic criteria, resides specifically at centromeric loci in vivo [2].
• We show that Mif2 is a critical in vivo target of the Aurora kinase Ipl1p [3].

Biological context of MIF2

• Here we provide genetic evidence that MIF2 encodes a centromere protein [4].
• Specifically, we found that mutations in MIF2 stabilize dicentric minichromosomes and confer high instability (i.e., a synthetic acentric phenotype) to chromosomes that bear a cis-acting mutation in element I of the yeast centromeric DNA (CDEI) [4].
• The MIF2 gene of Saccharomyces cerevisiae has been implicated in mitosis [4].
• The Mif2 and Cep1 proteins contain motifs of known transcription factors, suggesting that assembly of the yeast centromere is analogous to that of eukaryotic enhancers and origins of replication [4].
• When MIF2 was overexpressed, chromosomes missegregated during mitosis and cells accumulated in the G2 and M phases of the cell cycle [5].

Anatomical context of MIF2

• Studies using temperature-sensitive mutants showed that the loss of yeast Mif2 protein function results in chromosome missegregation, mitotic delay, and aberrant microtubule morphologies (2) [6].

Physical interactions of MIF2

• Taken together, these data suggest that the Mif2 protein interacts with Cep1p at the centromere and that the yeast centromere indeed exists as a higher order protein-DNA complex [4].

Other interactions of MIF2

• In addition, the mif2 temperature-sensitive phenotype can be partially rescued by increased dosage of CEP1 [4].
• A human HSMT3 cDNA encoding a homolog of the yeast SMT3, a suppressor of MIF2 mutations in a centromere protein gene, was identified and sequenced [7].
• A 17.5 kb DNA fragment of chromosome XI, located between the genetic loci mif2 and mak11 was sequenced and analysed [8].
• MIF2 is required for mitotic spindle integrity during anaphase spindle elongation in Saccharomyces cerevisiae [5].
• The sequence of PIC1 shows 52% identity to a S. cerevisiae ubiquitin-like protein that was cloned as a suppressor of mutations in MIF2, a protein required for mitotic spindle integrity during anaphase [9].

References