Establishment and dynamics of the centromere chromatin, which ensure the faithful genome inheritance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Osaka University
• Principal Investigator: Hori Tetsuya 大阪大学, 大学院生命機能研究科, 准教授 (70550078)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: セントロメア / クロマチン / エピジェネティックス / 細胞周期

Outline of Final Research Achievements

We found a critical CENP-A residue essential for faithful chromosome segregation. Moreover, we demonstrated that this residue was required for the proper complex formation with the CENP-A specific chaperon HJURP. Based on the structural analyses, we identified several contact sites of KNL2 to make a complex with CENP-A nucleosome, which was essential for the KNL2 localization and function. Furthermore, the artificial ectopic tethering assays indicated the additional CENP-A loading pathway depending on the CENP-C interaction with HJURP. These findings may provide insight into developing an anti-cancer drug utilizing centromeric chromatin modulation.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝情報の継承に重要な、細胞核内のセントロメアのクロマチンの形成の仕組みと、その安定維持を保証するメカニズムの一端を明らかにした。これら成果は、細胞の遺伝情報の伝播の仕組みを解明する鍵となる知見として期待される。さらに将来的には、これら成果を活用した抗がん剤などの新規薬剤開発研究への応用が期待される。