Nucleic Acids Research, Vol 27, Issue 22 4335-4343, Copyright © 1999 by Oxford University Press
H Oda, A Taketomi, R Maruyama, R Itoh, K Nishioka, H Yakushiji, T Suzuki, M Sekiguchi and Y Nakabeppu
The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase,
produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The
B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs
in their 5' regions. We report here that these transcripts produce three
forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation
reactions. Three polypeptides were also detected in extracts of human
cells, using western blotting. B-type mRNAs with a polymorphic alteration
(GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to
CGA yielding another in-frame AUG further upstream, produced an additional
polypeptide (p26) in vitro. Substitution of each AUG abolished the
production of each corresponding polypeptide. Cell lines from individuals
with the GC allele contain more B-type mRNAs than do those of GT
homozygotes, and the former produce all of four polypeptides but the latter
lack p26. Amounts of each polypeptide reflected copy number of the GC
allele in each cell line. There is an apparent linkage dis-equilibrium
between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at
codon 83 for p18.
ARTICLES
Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism
Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
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