Sequence similarities between the yeast chromosome segregation protein Mif2 and the mammalian centromere protein CENP-C

Abstract

A short stretch of strong homology between the Saccharomyces cerevisiae chromosome segregation protein Mif2 and the DNA-binding motifs of the Drosophila D1 and mammalian HMGI(Y) chromosomal proteins suggested that Mif2 may act directly on chromosomes. Because this conserved motif is involved in binding A.T DNA, it was proposed that Mif2 may interact with chromosomes at the highly A + T-rich DNA element found in yeast centromeres. Comparison of the Mif2 amino-acid sequence with sequence databases showed that Mif2 shares at least two regions of similarity with the mammalian centromere protein CENP-C, suggesting an evolutionary conservation of centromere protein function from yeast to mammals. The order, spacing and location of these regions are also similar in the two proteins. Sequence analysis of several conditional lethal alleles of MIF2 generated by random mutagenesis revealed mutations in regions homologous to CENP-C, as well as in the highly conserved A.T DNA-binding motif. A potential phosphorylation site for p34cdc2 kinase located adjacent to the A.T DNA-binding motif was also found to be mutated in one of the mutants, suggesting that phosphorylation at this site may be important for Mif2 function and possibly for DNA binding.