1991 Fiscal Year Final Research Report Summary
Analysis of mutations induced in cells derived from DNA repair-deficient hereditary disease patients.
| Project/Area Number |
02671046
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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 |
YAGI Takashi Kyoto University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80182301)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEBE Hiraku Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (10028318)
TATSUMI Junko Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (80128222)
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| Project Period (FY) |
1990 – 1991
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| Keywords | DNA repair / Mutation / xeroderma pigmentosum / Ataxia telangectasia / Cancer-prone disease / Ultraviolet light / Gamma ray |
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| Research Abstract |
To assess the contribution to mutagenesis by DAN repair defects, mutagen-treated shuttle vector plasmids were passed through fibroblasts derived from xeroderma pigmentosum(XP)patients in 3 different DNA repair complementation groups(A, C and F), ataxia telangectasia(AT)patients and mice.
In comparison to DNA repair proficient normal human cells, the UV-treated plasmed passed through the XP-A, C or F cells showed fewer surviving plasmids(XP-A less than C and F)and a higher frequency of mutated plasmids(XP-A greater than C and F). Among base substitution mutations, the major type of the substitution was G : C -> A : T transition in all 3 cell lines. The XP-A, C and F cells revealed a hlgher frequency of G : C -> A : T transition along with a lower frequency of transverslons compared to the normal line. The spectrum of mutations In the XP-A cells was similar to that in the XP-C and F cells. Most single base substitution mutations occurred at G : C base pairs in which the 5'-nelghboring base of the cytosine was a pyrimidine. In spontaneous mutants, more than 50% mutants have a deletion, and the rest have base substitutions with a high frequency of transversions. Among UV-Induced base substitution mutants from mouse cells, 91% mutants have G : C -> A : T transition. gamma -ray-irradiated plasmids passed through AT and normal cells showed no significant difference in the survival and a frequency of mutated plasmed. Efficiency of rejoining of vector DNA restricted by an endonuclease was similar between AT and normal cells, but fidelity of the rejoining is higher in the normal than AT cells. A frequency of methyl nitrosourea-induced mutations, especially G : C -> A : T transition was higher in O^6-alkylguanine-repair deficient mouse cells than the proficient mouse cells.
In this study, a role of DNA repair for the Induction of mutation in molecular level was clarified by using shuttle vectors and DNA repair deficient cells.
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