Molecular mechanisms of multiple regulation of post-replication repair pathway by deubiquitinases

Research Project

Project/Area Number	26550024
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Risk sciences of radiation and chemicals
Research Institution	Nagoya University
Principal Investigator	Masuda Yuji 名古屋大学, 医学系研究科(環医), 准教授 (30273866)
Project Period (FY)	2014-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	DNA損傷トレランス / DNA修復 / ユビキチン化PCNA / 脱ユビキチン酵素 / 損傷トレランス機構
Outline of Final Research Achievements	In humans, cells have two damage tolerance pathways. One is the error-prone pathway, translesion DNA synthesis (TLS). The other is the error-free, in principle, pathway, template switch (TS). These are regulated by ubiquitination of PCNA. Since mono- and poly-ubiquitination of PCNA stimulates TLS and TS, respectively, the regulation of pathway choice is a crucial step for the maintenance of genetic stability. However, in humans, the regulatory mechanism is obscure because poly-ubiquitinated PCNA is only slightly detectable. In this study, we identified deubiquitinases for ubiquitinated PCNA and analyzed their function in the damage tolerance pathways.