1997 Fiscal Year Final Research Report Summary
Molecular analysis of hereditary photo-sensitive disorders
| Project/Area Number |
08457631
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Kumamoto University |
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Principal Investigator |
YAMAIZUMI Masaru Kumamoto University School of Medicine, Professor, 医学部, 教授 (70107093)
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| Co-Investigator(Kenkyū-buntansha) |
TATEISHI Satoshi Kumamoto University School of Medicine, Reserach Associate, 医学部, 助手 (00227109)
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| Project Period (FY) |
1996 – 1997
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| Keywords | photo-sensitive disorder / DNA repair / XP-variant / XP-E / UV^sS syndrome |
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| Research Abstract |
Xeroderma pigmentosum (XP) is a typical photo-sensitive hereditary disorder. There are eight complementation groups in XP,including a variant from (XP-V). We have diagnosed more than 70 photosensitive patients based on our systematic diagnosis procedure. Among these patients, XP-V is the most frequent group and thus far cumulative number of XP-V patients is 10. We have obtained one XP-V cell line immortalized by SV40, which shows high UV-sensitivity in the presence of caffeine. To test whether there are subgroups in XP-V,we have isolated a double-drug resistant cell line (6-thioguanine and G418) from the immortalized cells and fused these cells with primary XP-V strains from 10 different patients. Hybrid cells were selected in HAT medium containing 6-TG.All of the hybrids were as sensitive as parent cells, suggesting single complementation group of XP-V.
One patient showing typical XP manifestations was found to be defective in a DNA-damage binding protein (DDB). Her DDB gene has two point mutations in homo at different sites. One mutation was a nonsense mutation in an exon, resulting in a short protein. Another mutation was in an intron, resulting in exon skip. Analysis of the DDB function is now under investigation.
p53 response in UV^sS cells was found to be induced with low doses of UV-irradiation like CS cells, leading to cell cycle arrest at G1/S.These results suggest an important role of transcription in the induction.
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