Mechanism of DNA synthesis-activated proteolysis for genome integrity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06547
• 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: University of Hyogo
• Principal Investigator: Nishitani Hideo 兵庫県立大学, 理学研究科, 教授 (40253455)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ゲノム情報 / DNA複製 / タンパク質分解 / Cdt2 / PCNA

Outline of Final Research Achievements

To maintain the genome information during successive cell division cycles, DNA replication is regulated so that it occurs only once in a cell cycle. When DNA replication starts, PCNA is loaded at a replication site and Cdt1 binds to it, which is targeted for degradation by CRL4-Cdt2 to prevent re-replication. In this process, the recruitment of CRL4-Cdt2 to PCNA must be correctly regulated. To address such a regulation, we adopted a live image analysis of Cdt2 recruitment to PCNA. We present evidence that PCNA-interacting motif plays a primal role of Cdt2 recruitment and that DNA binding domain and phosphorylation in Cdt2 fine tune its recruitment to PCNA.

Free Research Field

DNA複製制御

Academic Significance and Societal Importance of the Research Achievements

細胞機能が忠実に遂行されるためにはタンパク質の機能が正確に制御されなければならない。さらに、細胞の状態をセンスして制御する必要がある。CRL4-Cdt2はタンパク質分解に関わるユビキチンリガーゼで、S期が開始すると素早く有害となったタンパク質の分解に関わり、S期が終了すると次のサイクルのために分解機能が抑制される必要がある。我々の成果は、PCNAへの結合（集積）の制御を多重な方法で、また、効率よく制御する仕組みを通して、そのような制御機構を示すものである。