1990 Fiscal Year Final Research Report Summary
Analysis of Genes for DNA Replication Enzymes and Homeobox Proteins in Congenital Multiple Anomalies.
| Project/Area Number |
01480500
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human genetics
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| Research Institution | Tokai University School of Medicine |
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Principal Investigator |
MORIUCHI Tetsuya Tokai University School of Medicine Department of Cell Biology, Associate Professor, 医学部, 助教授 (20174394)
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| Co-Investigator(Kenkyū-buntansha) |
IWASAKI Katsuhiko Tokai University School of Medicine, Department of Obstetrics and Gynecology, As, 医学部, 助教授 (10119646)
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| Project Period (FY) |
1989 – 1990
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| Keywords | PCNA / DNA polymerase beta / gamma-crystalline / plant / Drosophila / DNA replication / Homeobox proteins / congenital anomalies |
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| Research Abstract |
1. DNA polymerase delta auxiliary protein (PCNA) and homeopox protein : We isolated genomic clones encoding rice PCNA and partially sequenced one of the clones. The rice amino acid sequence shared 60% homology with the sequence of the rat PCNA (P. N. A. S. 86 : 3189-3193, 1989). We also determined the c omplete nucleotide sequence of the Drosophila PCNA gene and found a cluster of putative binding sites for the homeodomain-containing gene products in the 5^,-flanking region. Footprint analysis revealed that Drosophila homeodomain proteins (even-skipped and zerknullt) can specifically bi these sites (M. C. B. 10 : 872-879, 1990). In order to demonstrate the close relationship between the regulation of developmentally programmed differentiation and that of cell proliferation in man, we isolated genomic clones for human PCNA and homeobox 4A.
2. Studies on genes for DNA replication enzyme and on homeobox genes in congenital anomalies : Abnormal restriction fragments were detected by DNA blot hybridization with PCNA, DNA polymerase beta and DNA polymerase alpha probes in one of 15 cases of congenital malformations. Abnormal restriction frgments were detected in one case of 95 normal individuals when DNA polymerase beta and gamma-crystalline were used as probes. DNA blot analysis using box 4A and 4B probes did not show any unusual restriction fragments in the DNA samples of congenital anomalies. Thirty DNA samples of severe degree of congenital malformations were examined for polymorphisms with gamma-crystalline DNA fragment which has been mapped near the homeobox 4 locus in chomosome
2. Statistically significant association was demonstrated between congenital malformations and RFLPs of gamma-crystalline ganes. This result indicates that the locus closely linked to congenital malformations is present in the proximity of gamma-crystalline and homeobox 4 loci (Nucleic Acids Symp. Ser. 21 : 19-20, 1989, IRL press).
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[Publications] Suzuka, I., Daidoji, H., Matsuoka, M., Kadowaki, K., Takasaki, Y., Nakane, P. K. and Moriuchi,T.: "Gene for proliferating-cell nuclear antigen (DNA polymerase delta auxiliary protein) is present in both mammalian and higher plant genomes." Proc.Natl.Academy.Sci.USA. 86. 3189-3193 (1989)
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[Publications] Moriuchi,T., Awataguchi, S., Taniguchi, Y., Iwasaki, K., Katabami, M., Naito, H., and Kuzumaki, N.: "A polymorphic DNA marker genetically linked to congenital malformations." Nucleic Acids Res. (Symp.Ser.). 21. 19-20 (1989)
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[Publications] Yamaguchi, M., Nishida, Y., Moriuchi,T., Hirose, F., Hui, C., Suzuki, Y. and Matsukage, A.: "Drosophila PCNA/cyclin gene ; Structure, expression during development, and specific binding of homeodomain proteins to its 5'-flanking region." Mol. Cell Bio.10(3). 872-879 (1990)
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