GENOMIC ORGANIZATION AND EXPRESSION OF THE HUMAN MSH3 GENE

We have studied the expression and genomic organization of the human M SH3 gene, which encodes a human homologue of the bacterial DNA mismatc h repair protein MutS. This gene is located upstream of the dihydrofol ate reductase (DHFR) gene. Northern analysis has demonstrated that the hMSH3 gene is expressed in a variety of human tissues at low levels, like the DHFR gene. Characterization of cosmid clones has shown that t he hMSH3 gene consists of 24 exons spanning at least 160 kb. All exon- intron junction sequences match the classical GT/AG rule, except that intron 6 has AT and AA at the ends. Two major transcripts of 5.0 and 3 .8 kb have been shown to be derived from the differential use of two p olyadenylation sites. Elucidation of the complete genomic organization and the nucleotide sequences of the introns of the hMSH3 gene should be useful for studying the function of this gene and the possible invo lvement of specific mutations of the hMSH3 gene in some diseases. (C) 1996 Academic Press, Inc.