Genome-stabilizing activity of aldehyde catalyzing enzymes that support epigenetic reprogramming

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K21394
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Takata Minoru 京都大学, 生命科学研究科, 特任教授 (30281728)
• Co-Investigator(Kenkyū-buntansha): 牟 安峰 京都大学, 生命科学研究科, 特定助教 (20894455)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: DNA 損傷 / ホルムアルデヒド / エピゲネティック再構築 / iPS 細胞 / ADH5 / ALDH2

Outline of Final Research Achievements

In this study, we attempted to verify that ADH5/ALDH2, a group of enzymes that degrade formaldehyde, is an essential mechanism underlying epigenome reconstruction. Inducible expression of ADH5 in ADH5/ALDH2 enzyme-deficient fibroblasts derived from patients with Aldehyde Degradation Deficiency Syndrome (ADDS), a novel genetic disease we discovered, clearly increased reprogramming efficiency to iPS cells. However, the addition of formaldehyde scavengers such as Dimedone or ALDH2 agonist drugs had little effect. Therefore, further investigation is needed to determine whether the effect of ADH5 on epigenetic reprogramming is by resolving formaldehyde degradation or not.

Free Research Field

分子生物学、DNA損傷応答

Academic Significance and Societal Importance of the Research Achievements

ホルムアルデヒド分解酵素ADH5やALDH2は、小児の重篤な遺伝病で骨髄不全症候群であるファンコニ貧血、さらに新規に見いだした類似の臨床所見を呈するADD症候群の、病態の根幹にあり、その疾患病態の解明と、新規治療法の開発に重要である。さらに、iPS細胞のりプログラミング効率化に役立つ可能性を秘めており、同細胞の臨床応用にも貢献できる可能性がある。