A germline mutation abolishing the original stop codon of the human adenine phosphoribosyltransferase (APRT) gene leads to complete loss of the enzyme protein |
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Authors: | Atsuo Taniguchi Masayuki Hakoda Hisashi Yamanaka Chihiro Terai Keiji Hikiji Ryuji Kawaguchi Noriko Konishi Sadao Kashiwazaki N Kamatani |
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Institution: | (1) Institute of Rheumatology, Tokyo Women’s Medical College, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan Fax: +81-3-5269-1726, JP;(2) Research and Development Center for Molecular Biology and Cytogenetics, SRL Laboratories, 51 Komiya-cho, Hachijoji-shi, Tokyo 192, Japan, JP;(3) Kyoto Miniren Daini Chuo Hospital, Asukai-cho 89, Tanaka, Sakyo-ku, Kyoto, Japan, JP |
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Abstract: | Adenine phosphoribosyltransferase (APRT) is a purine metabolic enzyme and a homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine
urolithiasis. Various germline abnormalities have been described, but we report here a unique type of germline mutation in
a homozygous individual (SY) who had excreted 2,8-dihydroxyadenine crystals. In SY, TCA was substituted for the physiological
stop codon TGA. This base substitution generates a new HinfI restriction site, and, using the polymerase chain reaction and subsequent digestion by this enzyme, it was confirmed that
SY is homozygous for the base substitution. This base change is unique in that it generates an open reading frame that extends
to the poly(A) addition site. The amount of mRNA in transformed B cells from SY was approximately a quarter of that in control
subjects and no APRT proteins were detected. In eukaryotes, unlike in prokaryotes, no rescue systems for defective polypeptide
termination caused by a missing stop codon have been found. Therefore, the outcome of the defect of SY is unclear from present
knowledge about termination of polypeptide synthesis. Investigations into the mechanisms of the absence of protein in the
cells of SY may lead to a better understanding of the physiological and nonphysiological termination of polypeptide synthesis
in eukaryotic cells.
Received: 26 August 1997 / Accepted: 5 November 1997 |
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