Analysis of functional crosstalk between Fanconi anemia proteins and aldehyde metabolism

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kobe University
• Principal Investigator: Sakai Wataru 神戸大学, バイオシグナル総合研究センター, 助教 (70526251)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ファンコニ貧血 / アルデヒド / 脂質代謝 / DNA損傷 / DNA修復

Outline of Final Research Achievements

Lipid is known as a source of various aldehydes that cause DNA damage such as DNA adduct and DNA crosslink. However, it still remains unclear how those genotoxic stresses are repaired and suppressed in the cell. This research project obtained a new possibility that one of the enzymes in lipid metabolism cooperates with the Fanconi anemia proteins (FA proteins) to prevent the occurrence of endogenous DNA damage. Surprisingly, a novel cellular dynamics of FA proteins were unveiled that some FA proteins translocates and accumulates onto surface of the organelle membranes in response to lipid metabolism. Detail molecular mechanism of this novel phenomenon is unknown, but this finding will contribute to the elucidation of the pathogenic mechanism of not only Fanconi anemia but also other diseases.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

希少遺伝疾患であるファンコニ貧血患者の多くが若年期から脂質代謝異常を示すことが報告されている。FAタンパク質のDNA損傷応答に関する研究・理解が進む一方、それらの発症機序については依然として不明な点が多い。本研究課題では一部のFAタンパク質が脂質代謝環境の変化に応答して細胞内での局在を変化させることを見出した。特に核内外に存在する細胞小器官周辺への局在変化はこれまで他に全く報告がなく特出すべき研究成果の一つである。今後はファンコニ貧血に見られる病態との関連性についても解析していく予定である。