Regulation of DNA replication through proteolysis coupled with PCNA cycle

2017 Fiscal Year Final Research Report

• Project/Area Number: 26291025
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: University of Hyogo
• Principal Investigator: Nishitani Hideo 兵庫県立大学, 生命理学研究科, 教授 (40253455)
• Co-Investigator(Kenkyū-buntansha): 塩見 泰史 兵庫県立大学, 生命理学研究科, 准教授 (80380567)
• Co-Investigator(Renkei-kenkyūsha): HAYASHI Akiyo 兵庫県立大学, 大学院生命理学研究科, 助教 (20779350)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: タンパク質分解 / ゲノムDNA / 複製 / 修復 / 細胞周期

Outline of Final Research Achievements

The CRL4-Cdt2 ubiquitin ligase plays an important role to prevent re-replication by targeting Cdt1 for degradation. In this project, we demonstrated that C-terminus of Cdt2 contributes to its association with PCNA upon initiation of S phase for rapid Cdt1 degradation. Purified proteins confirmed that the interaction is direct. On the other hand, Cdt2 is phosphorylated by cyclin-CDKs, which appeared to be important to inhibit its interaction with PCNA. Thus, CRL4-Cdt2 activity is regulated through the cell cycle. In addition, we showed that in response to UV damage, not only nucleotide repair but also mismatch repair participate in Cdt1 degradation for efficient repair of UV damages.

Free Research Field

分子生物学