| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Expression of Translin closely parallels the proliferative state in various cell types. Confocal microscopic analysis revealed that Translin is localized at the centrosomes at prophase and the mitotic spindle at metaphase, then translocating to the spindle midbodies during cytokinesis. The results suggest that Translin participates in processes ensuring the segregation of chromosomes and cytokinesis. Ataxia-telangiectasia (AT) is a recessive human genetic disorder resulting from mutations of Atm gene, characterized by progressive neuro-degeneration, immunologic defects, cancer predisposition, and hypersensitivity to ionizing radiation. AT cells show irradiation-induced cell-cycle checkpoint defects. To address the link between Translin and cell proliferation, we tested the Translin levels in Atm-deficient mice after exposure to ionizing radiation. The results clearly indicate that down-regulation of the Translin levels in spleen cells of wild mice, Atm(+/+), occurred within 24 hrs of irradiation, while those in Atm(-/-) mice did not change at all, consistent with the lack of cell-cycle arrest. Mice deficient in Translin are significantly smaller than control littermates and the lymphocyte development is arrested at the earliest progenitor stages. Since the nuclear matrix protein C1D, an activator of the DNA dependent protein kinase (DNA-PK), is known to affect the function of Translin, we are studying the repair mechanisms for the radiation-induced DNA damage in the mutant mice.
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