Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene.
The Escherichia coli MutHLS system has been highly conserved throughout evolution. The eukaryotic pathway results in a specialization of MutS homologs that have evolved to play crucial roles in both DNA mismatch repair and meiotic recombination. So far, meiosis-specific genes belonging to this family have only been identified in yeast. In Saccharomyces cerevisiae, MSH4 (MutS homolog 4) is a meiosis-specific protein that is not involved in mismatch correction. This protein is required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis I. We have identified the human MSH4 homolog gene. The predicted amino acid sequence shows 28.7% identity with the S. cerevisiae MSH4 protein. By Northern blot analysis, human MSH4 transcripts are only detectable in testis and in ovary with a lower level of expression. We have mapped MSH4 to human chromosome 1 at band p31 by fluorescence in situ hybridization. The identification of such a gene provides a powerful tool for clarifying the respective roles of MSH and MLH genes in mammalian meiosis.
Paquis-Flucklinger
V
V
Laboratoire de Neurobiologie Cellulaire, Laboratoire de Génétique Chromosomique des Tumeurs, UMR 6549 CNRS, Faculté de Médecine, Av. de Valombrose, Nice Cedex 2, 06107, France. paquis@unice.fr
Santucci-Darmanin
S
S
Paul
R
R
Saunières
A
A
Turc-Carel
C
C
Desnuelle
C
C
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C091158:MSH4 protein, S cerevisiae; C409221:MSH4 protein, human; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli