title: Isolation and characterization of the 5' region of the human mismatch repair gene hPMS1.
abstract: The hPMS1 gene encodes a mutL homolog that is implicated in DNA mismatch repair and was found to be mutated in the germline of a patient with hereditary nonpolyposis colorectal cancer (HNPCC). To understand transcriptional regulation and to perform mutational analysis in the promoter region, we cloned and characterized the genomic sequence of the 5' region of the gene. hPMS1 has an intron upstream of the initiation codon. There were several transcripts with alternative splicing sites and multiple transcriptional start sites. The cloned 1.4-kbp fragment of the 5' region contains a CpG island but no TATA-boxes, typical for promoters of housekeeping genes. The promoter activity of the fragment was almost equal to that of the SV40 early promoter. Deletion analysis showed that about a 300-bp region was sufficient to initiate transcription. Although we searched for mutations in the hPMS1 promoter region in HNPCC kindreds, neither germline nor somatic mutations were detected. However, we found a highly informative polymorphism in the first exon that is useful for searching allelic losses because no polymorphic changes in hPMS1 have been reported previously.
authors.affiliation: Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: E
authors.initials: E
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Iwahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yuasa
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification*; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D000070956:MutL Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D009363:Neoplasm Proteins; C088996:PMS1 protein, human; D000070956:MutL Proteins