| Project/Area Number |
06672258
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human genetics
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TATSUMI Junko Kyoto Univ., Graduate School of Medicine. Assistant Prof., 医学研究科, 助手 (80128222)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEBE Hiraku Kyoto Univ., Professor, 医学研究科, 教授 (10028318)
MIYAKOSHI Junji Kyoto Univ., Lecturer, 医学研究科, 講師 (70121572)
NISHIGORI Chikako Kyoto Univ., Asssistant Prof., 医学研究科, 助手 (50198454)
YAGI Takashi Kyoto Univ., Associate Prof., 医学研究科, 助教授 (80182301)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | xeroderma pigmentosum / DNA repair / inherited disease / mutation / skin cancer / ultraviolet light |
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| Research Abstract |
We searched for XPA-gene mutations by the restriction enzyme polymorphism in Japanese xeroderma pigmentosum group A (XP-A) patients. We found 56 AlwNI -/- (intron 3, G to C) patients, 4 AlwNI +/- and HphI -/+ (codon 228 C to T) patients, 2 AlwNI +/- and MseI -/+ (codon 116 T to A) patients, one AlwNI +/- and MaeII -/+ (codon 225 G to C) patient, one AlwNI -/- and MseI +/- patient and 2 HphI -/- patients.
We found an XP-A patient who is a compound heterozygote for the splicing mutation of the intron 3/exon 4 junction (AlwNI mutation), and a newly identified mutation at the last nucleotide of exon 5 (MaeII mutation). The new mutation leads to aberrant splicing, produces mRNA with deletion of 7 nucleotides and expresses a truncated XPA protein. The mild symptom of the patient may be due to the residual DNA repair activity of the truncated protein.
We try to detect an yet-unidentified XPF protein by immunological methods using an anti-ERCC1 antibody. A 120 KD band that bound to ERCC1 protein was detected in normal human cells but not in XPF cells, suggesting that the ERCC1 protein makes a complex with the XPF protein in normal cells but each protein alone is unstable in mutant cells.
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