Structure-function relationship of nucleo-protein machinery on specific genome

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Tokyo University of Science, Yamaguchi
• Principal Investigator: Kawakami Hironori 山陽小野田市立山口東京理科大学, 薬学部, 准教授 (50403952)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 染色体複製 / ORC / 機能構造解析 / DNA結合 / 高次複合体形成 / Cdc6

Outline of Final Research Achievements

The regulation of the replication initiator protein ORC by atypical DNA structures was analyzed in detail and new insights into the specificity of the binding ability of atypical DNA structures to ORC were found. In parallel, a biochemical method to elucidate the single-strand binding ability of ORC in detail in vitro was esablished. We also searched for genes that interact genetically with ORC, and during the course of this study, we obtained findings suggesting that multiple genes within a genomic clone cooperate directly or indirectly with the largest subunit Orc1 to inhibit the growth of budding yeast cells. Genomically co-localization sites with ORC (Genes Cells 2019) were further analyzed in detail and novel in silico findings were obtained.

Free Research Field

生物学

Academic Significance and Societal Importance of the Research Achievements

代表者独自のORC解析基盤を発展させることで、ORCのDNA結合能に関する特性や機能構造に加え、細胞内における結合能に関する新概念や発展性を示唆する可能性が提起された。これらの成果は、蛋白質とDNAとの結合メカニズムや制御という根本的問題の理解において重要な内容を含むことに加え、当該メカニズムの普遍性と多様性の理解をもたらすものと思われる。以上を踏まえ、当初の目的を十分達成することができたと判断した。