Molecular pathology and regulatory mechanisms involved in the breakdown of nucleotide pool homeostasis under environmental stress

2014 Fiscal Year Final Research Report

• Project/Area Number: 22221004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyushu University
• Principal Investigator: NAKABEPPU YUSAKU 九州大学, 生体防御医学研究所, 教授 (30180350)
• Co-Investigator(Kenkyū-buntansha): SAKUMI Kunihiko 九州大学, 生体防御医学研究所, 准教授 (50211933) ; TSUCHIMOTO Daisuke 九州大学, 生体防御医学研究所, 助教 (70363348) ; OKA Sugako 九州大学, 生体防御医学研究所, 学術研究員 (80467894) ; SHENG Zijing 九州大学, ヌクレオチドプール研究センター, 助教 (90467895) ; AKIMOTO Yoriko 九州大学, 生体防御医学研究所, 非常勤研究員 (50613254)
• Co-Investigator(Renkei-kenkyūsha): OHYAGI Yasumasa 九州大学, 医学研究院, 教授 (30301336)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 活性酸素 / 放射線 / DNA / RNA / 突然変異 / バイスタンダー効果 / 細胞死 / 神経変性

Outline of Final Research Achievements

We elucidated the importance of nucleotide pools as the targets of radiation and environmental stress as well as the biological significance of the quality control mechanisms for the nucleotide pools. Under the breakdown of nucleotide pool homeostasis, damaged nucleotides are incorporated into nuclear and mitochondrial genomes, and thus inducing mutagenesis, which results in carcinogenesis or congenital abnormalities. Damaged bases accumulated in genomes are efficiently removed by DNA repair mechanisms, however, persistent DNA repair induces programmed cell death. The cell death can contribute to suppression of carcinogenesis, while in brain or neural tissues the cell death rather causes neurodegeneration, such as Alzheimer's disease or retinal degeneration. Moreover, we revealed that damaged nucleosides released from the damaged cells act on adjacent cells, thus causing various bystander effects.

Free Research Field

生化学、分子生物学、神経科学