Grant-in-Aid for Scientific Research on Priority Areas.
|Research Institution||Tohoku University|
YASUI Akira Institute of Development, Aging and Cancer, Tohoku University, Professor, 加齢医学研究所, 教授 (60191110)
HAYAKAWA Hiroshi Faculty of Medicine, Kyusyu University, Assistant Professor, 医学部, 助手 (70150422)
TODO Tsuyoshi Radiation Biology Center, Kyoto University, Associate Professor, 放射線生物研究センター, 助教授 (90163948)
ENOMOTO Takemi Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80107383)
YAMAIZUMI Masaru Institute of Molecular Embryology and Genetics, Kumamoto University, Professor, 医学部, 教授 (70107093)
SEKI Syuji Faculty of Medicine, Okayama University, Professor, 医学部, 教授 (50032884)
|Project Fiscal Year
1993 – 1995
Completed(Fiscal Year 1996)
|Budget Amount *help
¥146,400,000 (Direct Cost : ¥146,400,000)
Fiscal Year 1995 : ¥60,000,000 (Direct Cost : ¥60,000,000)
Fiscal Year 1994 : ¥46,400,000 (Direct Cost : ¥46,400,000)
Fiscal Year 1993 : ¥40,000,000 (Direct Cost : ¥40,000,000)
|Keywords||DNA repair / protein structure / DNA damages / DNA binding protein / DNA修復 / 蛋白質の構造 / DNA損傷 / DNA結合蛋白質 / 修復酵素 / 分子生物学 / 遺伝情報 / 遺伝子 / 結晶化|
In this research project a number of novel DNA repair genes and proteins were isolated and structures of various repair proteins were determined as listed below ;
1) Cyclobutane pyrimidine dimer (CPD) photolyases from various higher eukaryotes including aplacental mammals and a 6-4photoproduct (64PP) photolyase gene from Drosophila melanogaster were firstly isolated. Novel UV endonuclease genes for CPD and 64PP was isolated from eukaryotes and a procaryote.
2) APEX (AP endonuclease) gene was isolated from mouse and its roles in DNA repair and development were identified.
3) A human gene encoding a RecQ homolog was isolated. Disruption of a yeast homolog of the cloned human gene gave a MMS sensitive, sporulation-deficient mutant.
4) A novel photosensitive human cell line like a Cockayne's syndrome (CS) was identified.
5) p53 protein was found to be induced in cell lines of CS of XPA with less UV dose than in XPC or HeLa cells. It was concluded that transcription block by UV damage activates p53.
6) An in vitro assay for NER was established using SV40 mini chromosome and used to isolate XPC and HHR23 genes. Furthermore, the association of both gene products was found to be essential for NER activity.
7) Structures of repair proteins, RUVC,XPA,T4 CPD glycosylase, 3-methyl adenine glycosylase and CPD photolyase, were firstly determined.