Elucidation of molecular mechanism for recruitment of SLX4 by BioID-based identification of novel interactors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12161
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Kyushu University (2022); Kyoto University (2020-2021)
• Principal Investigator: Katsuki Yoko 九州大学, 薬学研究院, 助教 (00645377)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ファンコニ貧血経路 / SLX4 / ユビキチン化 / BioID / フォーカス形成

Outline of Final Research Achievements

The gene encoding DNA repair protein SLX4 is a responsible gene of Fanconi anemia, and it is thought that SLX4 contributes to DNA interstrand crosslink (ICL) repair by localizing to the damage sites via its ubiquitin binding domain UBZ4. Previously, we identified RNF168 as an E3 ubiquitin ligase participating in the recruitment of SLX4 by siRNA screen using the N-terminal half of SLX4 (SLX4-N). In this study, proximity-dependent biotin identification (BioID) was performed in order to find the interacting factors with SLX4-N, and several components of the chromatin remodeling complex were discovered. Although the requirement of chromatin remodeling for ICL repair has been little studied, this finding indicates that chromatin remodeling factors may be involved in the localization of SLX4 to ICL sites in mammalian cells.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

これまでICL修復におけるクロマチン構造変換の重要性についてはあまり研究が進んでいなかった。DNAクロスリンク(ICL)修復の分子基盤の研究においては、アフリカツメガエルを用いたCell free システムを材料とした解析が最も進んでいるが、巨大なゲノムDNAと複雑に制御されたクロマチン高次構造を持つ哺乳類の複製ストレス応答にはクロマチン構造変換が必須であることが考えられる。本研究をさらに詳細に解析することで、ヒト細胞におけるICL修復の全体像の一端を明らかにすることができると考えられる。