Organization and expression of the mouse MTH1 gene for preventing transversion mutation.
An enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is present in various organisms and plays an important role in the control of spontaneous mutagenesis. The enzyme hydrolyzes 8-oxo-dGTP, an oxidized form of dGTP, to 8-oxo-dGMP, thereby preventing the occurrence of A:T to C:G transversion, caused by misincorporation. We isolated the mouse genomic sequence encoding the enzyme and elucidated its structure. The gene, named MTH1 for mutT homologue 1, is composed of at least five exons and spans approximately 9 kilobase pairs. A genomic region containing the pseudogene was also isolated. The promoter region for the gene is GC-rich, contains many AP-1 and AP-2 recognition sequences, and lacks a typical TATA box. Primer extension and S1 mapping analyses revealed the existence of multiple transcription initiation sites, among which a major site was defined as +1. The putative promoter region was placed upstream of the chloramphenicol acetyltransferase reporter gene, and control of expression of the gene was examined by introducing the construct into mouse NIH 3T3 cells. Deletion analysis indicated that a sequence from -321 to +9 carries the basic promoter activity while an adjacent region, spanning from +352 to +525 stimulates the frequency of transcription.
Igarashi
H
H
Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-82, Japan.
Tsuzuki
T
T
Kakuma
T
T
Tominaga
Y
Y
Sekiguchi
M
M
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D005656:Fungal Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D011544:Pseudogenes; D051381:Rats; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D005656:Fungal Proteins; C118806:MTH1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins