CLONING AND CHARACTERIZATION OF THE HUMAN AND CAENORHABDITIS-ELEGANS HOMOLOGS OF THE SACCHAROMYCES-CEREVISIAE MSH5 GENE

In Saccharomyces cerevisiae the MSH5 gene encoding a MutS homolog was identified as a gene required for meiotic crossing over. To understand the role of MSH5 in higher eukaryotes, we have identified both the hu man and the Caenorhabditis elegans MSH5 genes. The human and C. elegan s MSH5 predicted amino acid sequences share, respectively, 25.3 and 22 .0% identity with the S. cerevisiae MSH5 amino acid sequence. The huma n MSH5 gene consists of 25 exons and spans at least 12 kb of genomic D NA, while the C. elegans gene comprises 17 exons distributed over at l east 5.8 kb. Radiation hybrid mapping studies indicate that the human gene is located at 6p22.3-p21.3. Northern blot analysis demonstrates t hat human MSH5 is expressed to some extent in all tissues, but that pa rticularly high levels of expression occur in testis, thymus, and othe r tissues of the immune system. Two-hybrid interaction analysis demons trates that the human MSH4 and MSH5 proteins interact as observed for S. cerevisiae MSH4 and MSH5. (C) 1998 Academic Press.