Identification of oxidative stress defense and DNA repair proteins and elucidation of mechanisms of action

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K00545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: AKIYAMA QIUMEI (張秋梅) 京都大学, 理学研究科, 准教授 (00260604)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 酸化ストレス / DNA修復 / ヒト培養細胞 / 線虫C.eleganas / ストレス防御 / 放射線 / 大腸菌

Outline of Final Research Achievements

To elucidate the roles of DNA repair enzymes in multicellular C. elegans, double or triple deficient mutants of base excision repair enzymes (EXO-3, APN-1, UNG-1, NTH-1) were isolated, and we revealed their critical roles to prevent DNA damage and oxidative stress in C. elagans. These proteins were probed to play important roles on life span, growth and tissue formation. We also found that ATM is essential for the response to oxidative stress in non-dividing cells of C.elegans. Furthermore, we clarified the effects of ascidian APEX1 on embryogenesis, and the enzymatic activity of APEX2 was first identified in vitro. In the identification and functional analysis of cellular oxidative stress defense factors, we also found the critical function of Escherichia coli PqiABC in protection against oxidative stress, and we also revealed the human oxidative stress resistance protein OXR1 plays an important function in the radiation response and in maintaining genomic stability.

Free Research Field

放射線生物学, 分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、新規の酸化防御タンパク質やDNA修復酵素活性が同定され、それらを欠損あるいは発現抑制させた細胞や個体の性質が解明され、 損傷DNAの修復、抗酸化因子の酸化ストレス制御における役割がより明らかになった。酸化損傷修復の全体像の解明、寿命、 発生、成長、神経疾患における役割の理解に向けた新しい展開を促すことに大きく貢献できた。新しい酸化ストレス防御因子が同定でき、ストレス防御の全体像の理解にも大きく貢献した。この成果は酸化ストレスによる細胞の突然変異やがん化の抑制機構の解明にも貢献できる。